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Articles in press have been peer-reviewed and accepted, which are not yet assigned to volumes/issues, but are citable by Digital Object Identifier (DOI).
Construction and characterization of a full-length infectious clone of Getah virus in vivo
Tongwei Ren, Xiangling Min, Qingrong Mo, Yuxu Wang, Hao Wang, Ying Chen, Kang Ouyang, Weijian Huang, Zuzhang Wei
doi: 10.1016/j.virs.2022.03.007
Received: 02 September 2021 Accepted: 02 March 2022 Published: 11 March 2022
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Getah virus (GETV) is a mosquito-borne virus of the genus Alphavirus in the family Togaviridae and, in recent years, it has caused several outbreaks in animals. The molecular basis for GETV pathogenicity is not well understood. Therefore, a reverse genetic system of GETV is needed to produce genetically modified viruses for the study of the viral replication and its pathogenic mechanism. Here, we generated a CMV-driven infectious cDNA clone based on a previously isolated GETV strain, GX201808 (pGETV-GX). Transfection of pGETV-GX into BHK-21 cells resulted in the recovery of a recombinant virus (rGETV-GX) which showed similar growth characteristics to its parental virus. Then three-day-old mice were experimentally infected with either the parental or recombinant virus. The recombinant virus showed milder pathogenicity than the parental virus in the mice. Based on the established CMV-driven cDNA clone, subgenomic promoter and two restriction enzyme sites (BamHI and EcoRI) were introduced into the region between E1 protein and 3'UTR. Then the green fluorescent protein (GFP), red fluorescent protein (RFP) and improved light-oxygen-voltage (iLOV) genes were inserted into the restriction enzyme sites. Transfection of the constructs carrying the reporter genes into BHK-21 cells proved the rescue of the recombinant reporter viruses. Taken together, the establishment of a reverse genetic system for GETV provides a valuable tool for the study of the virus life cycle, and to aid the development of genetically engineered GETVs as vectors for foreign gene expression.
Construction and verification of an infectious cDNA clone of coxsackievirus B5
Lifang Song, Bopei Cui, Jinghuan Yang, Xiaotian Hao, Xujia Yan, Jialu Zhang, Dong Liu, Ziyang Song, Qian Wang, Qunying Mao, Zhenglun Liang
doi: 10.1016/j.virs.2022.03.005
Received: 07 September 2021 Accepted: 07 March 2022 Published: 11 March 2022
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Enteroviruses belonging to the family Picornaviridae are non-enveloped RNA viruses that cause hand-foot-mouth disease (HFMD), which can lead to severe neurological complications. Enteroviruses genomes represent a single open reading frame flanked by 5′-and 3′-untranslated terminal regions (UTRs), constituting the basis for classifying enteroviruses into groups A–D (Zaoutis et al., 1998). Current research is primarily focused on highly prevalent pathogens, including enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) of group A (Duan et al., 2021). However, group B viruses are also responsible for a significant number of infections that often cause histopathological changes in the heart, brain, and pancreas. For instance, coxsackievirus B5 (CV-B5) can induce aseptic meningitis, viral meningitis, acute flaccid paralysis, pancreatitis, and type I diabetes mellitus (Chen et al., 2020; Marcela et al., 2019; Hyöty et al., 2018). HFMD outbreaks caused by CV-B5 have been reported in China, Southeast Asia, and Europe. However, despite its clinical significance, little is known about its pathogenesis, and in-depth studies on the underlying mechanisms are urgently needed (Gao et al., 2018; Sciandra et al., 2020).
Regulation of antiviral immune response by African swine fever virus (ASFV)
Xiaojie Zheng, Shengming Nie, Wen-Hai Feng
doi: 10.1016/j.virs.2022.03.006
Received: 07 December 2021 Accepted: 07 March 2022 Published: 09 March 2022
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African swine fever (ASF) is a highly contagious and acute hemorrhagic viral disease with a high mortality approaching 100% in domestic pigs. ASF is an endemic in countries in sub-Saharan Africa. Now, it has been spreading to many countries, especially in Asia and Europe. Due to the fact that there is no commercial vaccine available for ASF to provide sustainable prevention, the disease has spread rapidly worldwide and caused great economic losses in swine industry. The knowledge gap of ASF virus (ASFV) pathogenesis and immune evasion is the main factor to limit the development of safe and effective ASF vaccines. Here, we will summarize the molecular mechanisms of how ASFV interferes with the host innate and adaptive immune responses. An in-depth understanding of ASFV immune evasion strategies will provide us with rational design of ASF vaccines.
Differential miRNA expression profiling of Highly Pathogenic Avian Influenza Virus H5N1 infected chicken lungs reveals critical microRNAs, biological pathways and genes involved in the molecular pathogenesis
Anamika Mishra, Muhasin Asaf, Amod Kumar, Diwakar Dattatreya Kulkarni, Richa Sood, Sandeep Bhatia, Bharat Bhushan, Ashwin Ashok Raut
doi: 10.1016/j.virs.2022.03.004
Received: 24 January 2021 Accepted: 07 March 2022 Published: 09 March 2022
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Avian influenza is a highly contagious viral infection affecting the respiratory system. MicroRNAs (miRNAs) are small, regulatory, endogenous, non-coding RNAs of ~22 nt that regulate the gene expression of the target mRNAs by cleavage or translational repression. miRNAs are connected with the host response during avian influenza virus (AIV) infection (Wang et al., 2009; Wang et al., 2012). In this study, we used miRNomics approach to understand the complex host-pathogen interaction during the HPAIV H5N1 infection in chicken.
Cytoplasmic domain and enzymatic activity of ACE2 are not required for PI4KB dependent endocytosis entry of SARS-CoV-2 into host cells
Hang Yang, Huijun Yuan, Xiaohui Zhao, Meng Xun, Shangrui Guo, Nan Wang, Bing Liu, Hongliang Wang
doi: 10.1016/j.virs.2022.03.003
Received: 10 November 2021 Accepted: 04 March 2022 Published: 07 March 2022
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The recent COVID-19 pandemic poses a global health emergency. Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2 (ACE2). Here, by using lentivirus based pseudotypes bearing spike protein, we demonstrated that entry of SARS-CoV-2 into host cells was dependent on clathrin-mediated endocytosis, and phosphoinositides played essential roles during this process. In addition, we showed that the intracellular domain and the catalytic activity of ACE2 were not required for efficient virus entry. Finally, we showed that the current predominant Delta variant, although with high infectivity and high syncytium formation, also entered cells through clathrin-mediated endocytosis. These results provide new insights into SARS-CoV-2 cellular entry and present proof of principle that targeting viral entry could be an effective way to treat different variant infections.
Consolidation treatment needed for sustained HBsAg-negative response induced by interferon-alpha in HBeAg positive chronic hepatitis B patients
Minghui Li, Fangfang Sun, Xiaoyue Bi, Yanjie Lin, Liu Yang, Yao Lu, Lu Zhang, Gang Wan, Wei Yi, Linqing Zhao, Yao Xie
doi: 10.1016/j.virs.2022.03.001
Received: 21 October 2021 Accepted: 25 February 2022 Published: 04 March 2022
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Hepatitis B surface antigen (HBsAg) clearance is considered as functional cure in patients with chronic hepatitis B (CHB). This study aimed to assess the durability of HBsAg clearance achieved by interferon-based therapies in patients with CHB who were originally positive for hepatitis B envelope antigen (HBeAg). In this prospective study, HBeAg-positive CHB patients with confirmed HBsAg loss under interferon-based therapies were enrolled within 12 weeks from end of treatment and followed up for 48 weeks. Virological markers, biochemical indicators, and liver imaging examinations were observed every 3–6 months. Sustained functional cure was analyzed as primary outcome. Factor associated with sustained HBsAg loss or reversion was also investigated. The rate of HBsAg loss sustainability was 91.8% (212/231). Patients receiving consolidation treatment for 12–24 weeks or ≥ 24 weeks had higher rates of sustained HBsAg negativity than those receiving consolidation treatment for < 12 weeks (98.3% and 91.2% vs. 86.7%, P = 0.068), and the former groups had significantly higher anti-HBs levels than the later (P < 0.05). The cumulative incidence of HBsAg reversion and HBV DNA reversion was 8.2% and 3.9%, respectively. Consolidation treatment of ≥ 12 weeks [odd ratio (OR) 3.318, 95% confidence interval (CI) 1.077–10.224, P = 0.037) was a predictor of sustained functional cure, and HBeAg-positivity at cessation of treatment (OR 12.271, 95% CI 1.076–139.919, P = 0.043) was a predictor of HBsAg reversion. Interferon-alpha induced functional cure was durable and a consolidation treatment of ≥ 12–24 weeks was needed after HBsAg loss in HBeAg-positive CHB patients.
Development of a fluorescent probe hydrolysis-insulated isothermal PCR for rapid and sensitive on-site detection of African swine fever virus
Tianli Zou, Junhua Deng, Xiangdong Li, Shiyin Zhang, Lingyan Chen, Liying Hao, Jinshan Zhuang, Heng Wang, Guihong Zhang, Shengxiang Ge, Kegong Tian
doi: 10.1016/j.virs.2022.03.002
Received: 11 November 2021 Accepted: 01 March 2022 Published: 04 March 2022
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African swine fever virus (ASFV), the sole member of the family Asfarviridae, is thecausative agent of African swine fever (ASF), a viral disease that leads to high mortality indomestic pigs. Since firstly identified in Kenya in the 1920s, ASFV has been prevalent inAfrica, Europe, and Russian Federation (Sanchez et al., 2019). Recently, ASFV wasintroduced to Asian countries including China, Mongolia, Vietnam, Cambodia, Laos andSouth Korea, which lead to huge economic losses to local pig industries (Li and Tian, 2018,Gaudreault and Richt, 2019). The first case of ASFV in China was reported in August 2018(Zhou et al., 2018). Since then, hundreds of cases in most provinces were officiallyannounced and more than 1 million pigs were slaughtered under the strict stamping-out policy(Miao et al., 2019).
Characterization of human IgM and IgG repertoires in individuals with chronic HIV-1 infection
Xiaolong Tian, Binbin Hong, Xiaoyi Zhu, Desheng Kong, Yumei Wen, Yanling Wu, Liying Ma, Tianlei Ying
doi: 10.1016/j.virs.2022.02.010
Received: 25 September 2021 Accepted: 24 February 2022 Published: 03 March 2022
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Advancements in high-throughput sequencing (HTS) of antibody repertoires (Ig-Seq) have unprecedentedly improved our ability to characterize the antibody repertoires on a large scale. However, currently, only a few studies explored the influence of chronic HIV-1 infection on human antibody repertoires and many of them reached contradictory conclusions, possibly limited by inadequate sequencing depth and throughput. To better understand how HIV-1 infection would impact humoral immune system, in this study, we systematically analyzed the differences between the IgM (HIV-IgM) and IgG (HIV-IgG) heavy chain repertoires of HIV-1 infected patients, as well as between antibody repertoires of HIV-1 patients and healthy donors (HH). Notably, the public unique clones accounted for only a negligible proportion between the HIV-IgM and HIV-IgG repertoires libraries, and the diversity of unique clones in HIV-IgG remarkably reduced. In aspect of somatic mutation rates of CDR1 and CDR2, the HIV-IgG repertoire was higher than HIV-IgM. Besides, the average length of CDR3 region in HIV-IgM was significant longer than that in the HH repertoire, presumably caused by the great number of novel VDJ rearrangement patterns, especially a massive use of IGHJ6. Moreover, some of the B cell clonotypes had numerous clones, and somatic variants were detected within the clonotype lineage in HIV-IgG, indicating HIV-1 neutralizing activities. The in-depth characterization of HIV-IgG and HIV-IgM repertoires enriches our knowledge in the profound effect of HIV-1 infection on human antibody repertoires and may have practical value for the discovery of therapeutic antibodies.
Efficient assembly of a large fragment of monkeypox virus genome as a qPCR template using dual-selection based transformation-associated recombination
Lei Yang, Lingqian Tian, Leshan Li, Qiuhong Liu, Xiang Guo, Yuan Zhou, Rongjuan Pei, Xinwen Chen, Yun Wang
doi: 10.1016/j.virs.2022.02.009
Received: 10 August 2021 Accepted: 23 February 2022 Published: 28 February 2022
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Transformation-associated recombination (TAR) has been widely used to assemble large DNA constructs. One of the significant obstacles hindering assembly efficiency is the presence of error-prone DNA repair pathways in yeast, which results in vector backbone recircularization or illegitimate recombination products. To increase TAR assembly efficiency, we prepared a dual-selective TAR vector, pGFCS, by adding a PADH1-URA3 cassette to a previously described yeast-bacteria shuttle vector, pGF, harboring a PHIS3-HIS3 cassette as a positive selection marker. This new cassette works as a negative selection marker to ensure that yeast harboring a recircularized vector cannot propagate in the presence of 5-fluoroorotic acid. To prevent pGFCS bearing ura3 from recombining with endogenous ura3-52 in the yeast genome, a highly transformable Saccharomyces cerevisiae strain, VL6-48B, was prepared by chromosomal substitution of ura3-52 with a transgene conferring resistance to blasticidin. A 55-kb genomic fragment of monkeypox virus encompassing primary detection targets for quantitative PCR was assembled by TAR using pGFCS in VL6-48B. The pGFCS-mediated TAR assembly showed a zero rate of vector recircularization and an average correct assembly yield of 79% indicating that the dual-selection strategy provides an efficient approach to optimizing TAR assembly.
Human cytomegalovirus RNA2.7 inhibits RNA polymerase II (Pol II) Serine-2 phosphorylation by reducing the interaction between Pol II and phosphorylated cyclin-dependent kinase 9 (pCDK9)
Yujing Huang, Xin Guo, Jing Zhang, Jianming Li, Mingyi Xu, Qing Wang, Zhongyang Liu, Yanping Ma, Ying Qi, Qiang Ruan
doi: 10.1016/j.virs.2022.02.011
Received: 12 August 2021 Accepted: 24 February 2022 Published: 28 February 2022
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Human cytomegalovirus (HCMV) is a ubiquitous pathogen belongs to beta herpesvirus family. RNA2.7 is a highly conserved long non-coding RNA accounting for more than 20% of total viral transcripts. In our study, functions of HCMV RNA2.7 were investigated by comparison of host cellular transcriptomes between cells infected with HCMV clinical strain and RNA2.7 deleted mutant. It was demonstrated that RNA polymerase II (Pol II)-dependent host gene transcriptions were significantly activated when RNA2.7 was removed during infection. A 145 nt-in-length motif within RNA2.7 was identified to inhibit the phosphorylation of Pol II Serine-2 (Pol II S2) by reducing the interaction between Pol II and phosphorylated cyclin-dependent kinase 9 (pCDK9). Due to the loss of Pol II S2 phosphorylation, cellular DNA pre-replication complex (pre-RC) factors, including Cdt1 and Cdc6, were significantly decreased, which prevented more cells from entering into S phase and facilitated viral DNA replication. Our results provide new insights of HCMV RNA2.7 functions in regulation of host cellular transcription.
Genomics and Proteomics of Apis mellifera Filamentous Virus Isolated from Honeybees in China
Dahe Yang, Jun Wang, Xi Wang, Fei Deng, Qingyun Diao, Manli Wang, Zhihong Hu, Chunsheng Hou
doi: 10.1016/j.virs.2022.02.007
Received: 22 October 2021 Accepted: 21 February 2022 Published: 25 February 2022
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Apis mellifera filamentous virus (AmFV) is a large DNA virus that is endemic in honeybee colonies. The genome sequence of the AmFV Swiss isolate (AmFV CH-C05) has been reported but so far very few molecular studies have been conducted on this virus. We isolated and purified AmFV (AmFV CN) from Chinese honeybee (Apis mellifera) colonies and elucidated its genomics and proteomics. Electron microscopy showed ovoid purified virions with dimensions of 300–500 × 210–285 nm, wrapping a 3165 × 40 nm filamentous nucleocapsid in three figure-eight loops. Unlike AmFV CH-C05, which was reported to have a circular genome, our data suggest that AmFV CN has a linear genome of approximately 493 kb. A total of 197 ORFs were identified, among which 36 putative genes including18 homologs were annotated. The overall nucleotide similarity between the CN and CH-C05 isolates was 96.9%. Several ORFs were newly annotated in AmFV CN, including homologs of per os infectivity factor 4 (PIF4) and a putative integrase. Phylogenomic analysis placed AmFVs on a separate branch within the newly proposed virus class Naldaviricetes. Proteomic analysis revealed 47 AmFV virion-associated proteins, of which 14 had over 50% sequence coverage, suggesting that they are likely to be main structural proteins. In addition, all six of the annotated PIFs (PIF-0–5) were identified by proteomics, suggesting that they may function as entry factors in AmFV infection. This study provides fundamental information regarding the molecular biology of AmFV.
A single dose of recombinant VSV-RABVG vaccine provides full protection against RABV challenge
Minglong Liang, Zongmei Wang, Chuanjian Wu, Sidong Xiong, Ling Zhao, Chunsheng Dong
doi: 10.1016/j.virs.2022.02.008
Received: 20 July 2021 Accepted: 23 February 2022 Published: 25 February 2022
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Rabies virus (RABV) is an enveloped, non-segmented, and single-stranded RNA virus that belongs to the genus Lyssavirus within the Rhabdoviridae family (Douglas et.al., 2013). RABV causes rabies, and although vaccines are available, rabies continues to be a global public health concern causing more than 60,000 human deaths each year (WHO, 2013). There is a high prevalence especially in developing countries in Asia and Africa (Hampson et al., 2015; Singh et al., 2017). In most cases, RABV is transmitted through the direct contact of broken skin or the mucous membrane with the saliva of infected dogs. Unless the wound is promptly cleaned and post-exposure prophylaxis is administered, the human victim may develop encephalitis that is nearly always fatal.
Enterovirus 71 3C proteolytically processes the histone H3 N-terminal tail during infection
Meng Miao, Gang Deng, Xiaobei Xiong, Yang Qiu, Wenda Huang, Meng Yuan, Fei Yu, Shimei Bai, Xi Zhou, Xiaolu Zhao
doi: 10.1016/j.virs.2022.02.006
Received: 25 March 2021 Accepted: 16 February 2022 Published: 18 February 2022
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Enterovirus 71 (EV71) belongs to the genus Enterovirus, family Picornaviridae (Oberste et al., 1999). It was first isolated from patients with central nervous system diseases in California between 1969 and 1974 (Schmidt et al., 1974) and has spread worldwide (Solomon et al., 2010). EV71 infection usually causes mild, self-limiting hand, foot, and mouth disease in children. Acute EV71 infection may also cause severe polio-like neurological diseases and significant mortality. The spectrum of EV71-associated neurological diseases includes aseptic meningitis, brainstem and/or cerebellar encephalitis, acute flaccid paralysis (AFP), myocarditis, and rapid fatal pulmonary edema and hemorrhage (McMinn, 2002).
Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants
Jia Lu, Qiangling Yin, Rongjuan Pei, Qiu Zhang, Yuanyuan Qu, Yongbing Pan, Lina Sun, Ding Gao, Cuiqin Liang, Jingwen Yang, Wei Wu, Jiandong Li, Zongqiang Cui, Zejun Wang, Xinguo Li, Dexing Li, Shiwen Wang, Kai Duan, Wuxiang Guan, Mifang Liang, Xiaoming Yang
doi: 10.1016/j.virs.2022.02.005
Received: 23 January 2022 Accepted: 16 February 2022 Published: 18 February 2022
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Multiple new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have constantly emerged, as the delta and omicron variants, which have developed resistance to currently gained neutralizing antibodies. This highlights a critical need to discover new therapeutic agents to overcome the variants mutations. Despite the availability of vaccines against coronavirus disease 2019 (COVID-19), the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-CoV-2 variants infection. Here, we show that the nasal delivery of two previously characterized broadly neutralizing antibodies (F61 and H121) protected K18-hACE2 mice against lethal challenge with SARS-CoV-2 variants. The broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain (WIV04) and multiple variants, including beta (B.1.351), delta (B.1.617.2), and omicron (B.1.1.529) at 200 or 1000 TCID50, and the minimum antibody administration doses (5–1.25 mg/kg body weight) were also evaluated with delta and omicron challenge. Fully prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 mg/kg body weight, and corresponding mice lung viral RNA showed negative, with almost all alveolar septa and cavities remaining normal. Furthermore, low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants, whereas the F61/H121 combination showed excellent results against omicron infection. Our findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-CoV-2 variants infection.
Molecular and Serological Surveillance of Getah Virus in the Xinjiang Uygur Autonomous Region, China, 2017-2020
Ning Shi, Xiangshu Qiu, Xinyu Cao, Zhanhai Mai, Xiangyu Zhu, Nan Li, He Zhang, Jinyong Zhang, Zhuoxin Li, Nuerlan Shaya, Huijun Lu, Ningyi Jin
doi: 10.1016/j.virs.2022.02.004
Received: 19 July 2021 Accepted: 10 February 2022 Published: 14 February 2022
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The Getah virus (GETV), a mosquito-borne RNA virus, is widely distributed in Oceania and Asia. GETV is not only pathogenic to horses, pigs, cattle, foxes and boars, but it can also cause fever in humans. Since its first reported case in Chinese mainland in 2017, the number of GETV-affected provinces has increased to seventeen till now. Therefore, we performed an epidemiologic investigation of GETV in the Xinjiang region, located in northwestern China, during the period 2017–2020. ELISA was used to analyze 3299 serum samples collected from thoroughbred horse, local horse, sheep, goat, cattle, and pigs, with thoroughbred horse (74.8%), local horse (67.3%), goat (11.7%), sheep (10.0%), cattle (25.1%) and pigs (51.1%) being positive for anti-GETV antibodies. Interestingly, the neutralizing antibody titer in horses was much higher than in other species. Four samples from horses and pigs were positive for GETV according to RT-PCR. Furthermore, from the serum of a local horse, we isolated GETV which was designated as strain XJ-2019-07, and determined its complete genome sequence. From the phylogenetic relationships, it belongs to the Group III lineage. This is the first evidence of GETV associated to domestic animals in Xinjiang. Overall, GETV is prevalent in Xinjiang and probably has been for several years. Since no vaccine against GETV is available in China, detection and monitoring strategies should be improved in horses and pigs, especially imported and farmed, in order to prevent economic losses.
Identification and Genetic Characterization of Bovine Hepacivirus in China: A Large Scale Epidemiological Study
Gang Lu, Chaoxi Chen, Ran Shao, Juan Zhang, Jinghao Li, Siqi Cai, Lintao Zhong, Zhiying Lai, Jiajun Ou, Xin Yin, Guihong Zhang, Shoujun Li
doi: 10.1016/j.virs.2022.02.003
Received: 24 May 2021 Accepted: 10 February 2022 Published: 12 February 2022
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Bovine hepacivirus (BovHepV) is a novel virus that was recently discovered in Ghana and Germany in 2015. Until now, this virus has been identified in cattle population worldwide and is classified into subtypes A–G. To fully understand the epidemic situation and genetic characteristic of BovHepV in China, a total of 612 cattle serum samples were collected from 20 farms in seven provinces and municipality in China between 2018 and 2020 and were tested for the presence of BovHepV RNA via semi-nested PCR. The results demonstrated that 49 (8.0%) samples were BovHepV RNA-positive. It is noted that BovHepV infection in yak was confirmed for the first time. BovHepV was detected in all the seven provinces, with the positive rate ranging from 3.1% to 13.3%, which indicates a wide geographical distribution pattern of BovHepV in China. Sequencing results revealed that 5′ UTR of the 49 field BovHepV strains have a nucleotide similarity of 96.3%–100% between each other and 93.9%–100% with previously reported BovHepV strains. In addition, genetic analysis identified five critical nucleotide sites in 5′ UTR to distinguish different subtypes, which was further verified by genomic sequencing and nucleotide similarity analysis. All the 49 Chinese field BovHepV strains were classified into subtype G and this subtype is only determined in cattle in China currently. This study will provide insights for us to better understand the epidemiology and genetic diversity of BovHepV.
Ungulate bocaparvovirus 4 and rodent bocavirus are different genotypes of the same species of virus
Wenqiao He, Yuhan Gao, Yuqi Wen, Xuemei Ke, Zejin Ou, Jiaqi Fu, Mingji Cheng, Yun Mo, Qing Chen
doi: 10.1016/j.virs.2022.02.002
Received: 07 April 2021 Accepted: 10 February 2022 Published: 12 February 2022
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Bocaviruses are associated with many human infectious diseases, such as respiratory tract infections, gastroenteritis, and hepatitis. Rats are known to be reservoirs of bocaviruses, including rodent bocavirus and rat bocavirus. Recently, ungulate bocaparvovirus 4, a known porcine bocavirus, has also been found in rats. Thus, investigating bocaviruses in rats is important for determining the origin of the viruses and preventing and controlling their transmission. To the best of our knowledge, no study to date has investigated bocaviruses in the livers of rats. In this report, a total of 624 rats were trapped in southern China between 2014 and 2017. Liver and serum samples from rats were tested for the prevalence of bocaviruses using PCR. Sequences related to ungulate bocaparvovirus 4 and rodent bocavirus were detected in both liver and serum samples. Interestingly, the prevalence of ungulate bocaparvovirus 4 (reference strain: KJ622366.1) was higher than that of rodent bocavirus (reference strain: KY927868.1) in both liver (2.24% and 0.64%, respectively) and serum samples (2.19% and 0.44%, respectively). The NS1 regions of ungulate bocaparvovirus 4 and rodent bocavirus related sequences displayed over 84% and 88% identity at the nucleic and amino acid levels, respectively. Furthermore, these sequences had similar genomic structure, genomic features, and codon usage bias, and shared a common ancestor. These viruses also displayed greater adaptability to rats than pigs. Our results suggested that ungulate bocaparvovirus 4 and rodent bocavirus may originate from rats and may be different genotypes of the same bocavirus species.
Infection and pathogenesis of the Delta variant of SARS-CoV-2 in Rhesus macaque
Ge Gao, Xue Hu, Yiwu Zhou, Juhong Rao, Xiaoyu Zhang, Yun Peng, Jiaxuan Zhao, Yanfeng Yao, Kunpeng Liu, Mengying Liang, Hang Liu, Fei Deng, Han Xia, Chao Shan, Zhiming Yuan
doi: 10.1016/j.virs.2022.02.001
Received: 03 December 2021 Accepted: 24 January 2022 Published: 10 February 2022
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COVID-19 caused by SARS-CoV-2, is still a big threat to human populations around the world. As of Jan 2022, over 292 million cases were reported worldwide with more than 5.4 million deaths. After it was first reported in China in December 2019, the virus kept circulating and evolving and several variants with different transmissibility emerged in different countries and regions (WHO, 2021a). Until now, six major variants have been reported including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (C.37), and Omicron (B.1.1.529) and the infection caused by different variants has varied according to the surveillance data (WHO, 2021b).
The mutational dynamics of the SARS-CoV-2 virus in serial passages in vitro
Sissy Therese Sonnleitner, Stefanie Sonnleitner, Eva Hinterbichler, Hannah Halbfurter, Dominik B.C. Kopecky, Stephan Koblmüller, Christian Sturmbauer, Wilfried Posch, Gernot Walder
doi: 10.1016/j.virs.2022.01.029
Received: 26 September 2021 Accepted: 21 January 2022 Published: 29 January 2022
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Since its outbreak in 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) keeps surprising the medical community by evolving diverse immune escape mutations in a rapid and effective manner. To gain deeper insight into mutation frequency and dynamics, we isolated ten ancestral strains of SARS-CoV-2 and performed consecutive serial incubation in ten replications in a suitable and common cell line and subsequently analysed them using RT-qPCR and whole genome sequencing. Along those lines we hoped to gain fundamental insights into the evolutionary capacity of SARS-CoV-2 in vitro. Our results identified a series of adaptive genetic changes, ranging from unique convergent substitutional mutations and hitherto undescribed insertions. The region coding for spike proved to be a mutational hotspot, evolving a number of mutational changes including the already known substitutions at positions S:484 and S:501. We discussed the evolution of all specific adaptations as well as possible reasons for the seemingly inhomogeneous potential of SARS-CoV-2 in the adaptation to cell culture. The combination of serial passage in vitro with whole genome sequencing uncovers the immense mutational potential of some SARS-CoV-2 strains. The observed genetic changes of SARS-CoV-2 in vitro could not be explained solely by selectively neutral mutations but possibly resulted from the action of directional selection accumulating favourable genetic changes in the evolving variants, along the path of increasing potency of the strain. Competition among a high number of quasi-species in the SARS-CoV-2 in vitro population gene pool may reinforce directional selection and boost the speed of evolutionary change.
Isolation and characterization of a novel linear-plasmid phage from the sediment of the Mariana Trench
Yali Hao, Siyuan Wang, Mujie Zhang, Qingxue Tang, Canxing Meng, Liping Wang, Qilian Fan, Yaxian Yan, Xiang Xiao, Huahua Jian
doi: 10.1016/j.virs.2022.01.022
Received: 23 June 2021 Accepted: 20 October 2021 Published: 28 January 2022
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Temperate bacteriophages are widely distributed in bacteria isolated from different natural environments (Howard-Varona et al., 2017). The phages normally lead to lysogenic infection and merge their genetic components into the bacterial chromosome. Among the temperate phages, linear plasmid phages are atypical because of their capability to reside in host cells as linear dsDNA with covalently closed ends, rather than being integrated in host genomes in the form of prophages (Ravin et al., 2000; Ravin, 2011). The life cycle of N15, the first isolated linear plasmid phage, has been thoroughly investigated in its host Escherichia coli (Ravin, 2011). The formation of the linear plasmid prophage is attributed to a protelomerase that is encoded by the telN gene. The protelomerase acts on an inverted repeat site (telRL) on the phage genome, and then forms two covalently closed ends (telR and telL) (Ravin, 2003). Similar to phage λ DNA, N15 phage DNA has two 12-bp single-stranded cohesive ends (cosR and cosL), which are also responsible for the formation of the linear plasmid prophage of N15 (Ravin, 2015). Additionally, a multifunctional replication protein, RepA, which combines primase, helicase and DNA-binding activities, is indispensable for the lytic replication of N15 (Ravin, 2015).
An mRNA vaccine encoding Chikungunya virus E2-E1 protein elicits robust neutralizing antibody responses and CTL immune responses
Ningning Ge, Jin Sun, Zhihua Liu, Jiayi Shu, Huiming Yan, Zhihua Kou, Yu Wei, Xia Jin
doi: 10.1016/j.virs.2022.01.032
Received: 07 October 2020 Accepted: 24 January 2022 Published: 28 January 2022
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Arthropod-borne chikungunya virus (CHIKV) infection can cause a debilitating arthritic disease in human. However, there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical use. Here, we developed an mRNA-lipid nanoparticle (mRNA-LNP) vaccine expressing CHIKV E2-E1 antigen, and compared its immunogenicity with soluble recombinant protein sE2-E1 antigen expressed in S2 cells. For comparison, we first showed that recombinant protein antigens mixed with aluminum adjuvant elicit strong antigen-specific humoral immune response and a moderate cellular immune response in C57BL/6 mice. Moreover, sE2-E1 vaccine stimulated 12–23 folds more neutralizing antibodies than sE1 vaccine and sE2 vaccine. Significantly, when E2-E1 gene was delivered by an mRNA-LNP vaccine, not only the better magnitude of neutralizing antibody responses was induced, but also greater cellular immune responses were generated, especially for CD8+ T cell responses. Moreover, E2-E1-LNP induced CD8+ T cells can perform cytotoxic effect in vivo. Considering its better immunogenicity and convenience of preparation, we suggest that more attention should be placed to develop CHIKV E2-E1-LNP mRNA vaccine.
Recombinant human interferon-α1b inhibits SARS-CoV-2 better than interferon-α2b in vitro
Danrong Shi, Keda Chen, Xiangyun Lu, Linfang Cheng, Tianhao Weng, Fumin Liu, Nanping Wu, Lanjuan Li, Hangping Yao
doi: 10.1016/j.virs.2022.01.031
Received: 20 February 2021 Accepted: 21 January 2022 Published: 25 January 2022
Abstract PDF ScienceDirect ESM
The coronavirus disease 2019 (COVID-19) outbreak, has spread across the world (Wu et al., 2020). The causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly pathogenic and infectious, which become a major public health hazard that has had a devastating social and economic impact worldwide (Li QQ et al., 2020).
Psoralen inhibits hepatitis B viral replication by down-regulating the host transcriptional machinery of viral promoters
Xinna Ma, Heng Li, Ying Gong, Feifei Liu, Xiankun Tong, Fenghua Zhu, Xiaoqian Yang, Li Yang, Jianping Zuo
doi: 10.1016/j.virs.2022.01.027
Received: 30 May 2021 Accepted: 18 October 2021 Published: 25 January 2022
Abstract PDF ScienceDirect ESM
The hepatitis B virus (HBV) is a global public health challenge due to its highly contagious nature. It is estimated that almost 300 million people live with chronic HBV infection annually. Although nucleoside analogs markedly reduce the risk of liver disease progression, the analogs do not fully eradicate the virus. As such, new treatment options and drugs are urgently needed. Psoralen is a nourishing monomer of Chinese herb and is known to inhibit virus replication and inactivate viruses. In this study, we evaluated the potential of psoralen as an anti-HBV agent. Quantitative PCR and Southern blot analysis revealed that psoralen inhibited HBV replication in HepG2.2.15 cells in a concentration-dependent manner. Moreover, psoralen was also active against the 3TC/ETV-dual-resistant HBV mutant. Further investigations revealed that psoralen suppressed both HBV RNA transcription and core protein expression. The transcription factor FOXO1, a known target for PGC1α co-activation, binds to HBV pre-core/core promoter enhancer II region and activates HBV RNA transcription. Co-immunoprecipitation showed that psoralen suppressed the expression of FOXO1, thereby decreasing the binding of FOXO1 co-activator PGC1α to the HBV promoter. Overall, our results demonstrate that psoralen suppresses HBV RNA transcription by down-regulating the expression of FOXO1 resulting in a reduction of HBV replication.
Characteristics of SARS-CoV-2 transmission in a medium-sized city with traditional communities during the early COVID-19 epidemic in China
Yang Li, Hao-Rui Si, Yan Zhu, Nan Xie, Bei Li, Xiang-Ping Zhang, Jun-Feng Han, Hong-Hong Bao, Yong Yang, Kai Zhao, Zi-Yuan Hou, Si-Jia Cheng, Shuan-Hu Zhang, Zheng-Li Shi, Peng Zhou
doi: 10.1016/j.virs.2022.01.030
Received: 23 October 2021 Accepted: 21 January 2022 Published: 25 January 2022
Abstract PDF ScienceDirect
The nationwide COVID-19 epidemic ended in 2020, a few months after its outbreak in Wuhan, China at the end of 2019. Most COVID-19 cases occurred in Hubei Province, with a few local outbreaks in other provinces of China. A few studies have reported the early SARS-CoV-2 epidemics in several large cities or provinces of China. However, information regarding the early epidemics in small and medium-sized cities, where there are still traditionally large families and community culture is more strongly maintained and thus, transmission profiles may differ, is limited. In this study, we characterized 60 newly sequenced SARS-CoV-2 genomes from Anyang as a representative of small and medium-sized Chinese cities, compared them with more than 400 reference genomes from the early outbreak, and studied the SARS-CoV-2 transmission profiles. Genomic epidemiology revealed multiple SARS-CoV-2 introductions in Anyang and a large-scale expansion of the epidemic because of the large family size. Moreover, our study revealed two transmission patterns in a single outbreak, which were attributed to different social activities. We observed the complete dynamic process of single-nucleotide polymorphism development during community transmission and found that intrahost variant analysis was an effective approach to studying cluster infections. In summary, our study provided new SARS-CoV-2 transmission profiles representative of small and medium-sized Chinese cities as well as information on the evolution of SARS-CoV-2 strains during the early COVID-19 epidemic in China.
Genomic surveillance of coxsackievirus A10 reveals genetic features and recent appearance of genogroup D in Shanghai, China, 2016–2020
Jiayu Wang, Jiajing Liu, Fanghao Fang, Jiajin Wu, Tianjiao Ji, Yuying Yang, Ling Liu, Chongshan Li, Wanju Zhang, Xi Zhang, Zheng Teng
doi: 10.1016/j.virs.2022.01.028
Received: 17 September 2021 Accepted: 14 January 2022 Published: 24 January 2022
Abstract PDF ScienceDirect
Coxsackievirus A10 (CVA10) is one of the major causative agents of hand, foot and mouth disease (HFMD). To investigate the epidemiological characteristics as well as genetic features of CVA10 currently circulating in Shanghai, China, we collected a total of 9,952 sporadic HFMD cases from January 2016 to December 2020. In the past five years, CVA10 was the fourth prevalent causatives associated with HFMD in Shanghai and the overall positive rate was 2.78%. The annual distribution experienced significant fluctuations over the past five years. In addition to entire VP1 sequencing, complete genome sequencing and recombination analysis of CVA10 isolates in Shanghai were further performed. A total of 64 near complete genomes and 11 entire VP1 sequences in this study combined with reference sequences publicly available were integrated into phylogenetic analysis. The CVA10 sequences in this study mainly belonged to genogroup C and presented 91%–100% nucleotide identity with other Chinese isolates based on VP1 region. For the first time, our study reported the appearance of CVA10 genogroup D in Chinese mainland, which had led to large-scale outbreaks in Europe previously. The recombination analysis showed the recombination break point located between 5,100 nt and 6,700 nt, which suggesting intertypic recombination with CVA16 genogroup D. To conclusion, CVA10 genogroup C was the predominant genogroup in Shanghai during 2016–2020. CVA10 recombinant genogroup D was firstly reported in circulating in Chinese mainland. Continuous surveillance is needed to better understand the evolution relationships and transmission pathways of CVA10 to help to guide disease control and prevention.
Identification of Two Novel B-Cell Epitopes on the Nucleocapsid Protein of Porcine Deltacoronavirus
Haojie Ren, Xiaoguang Yan, Lintao Liu, Yixuan Zhang, Qianqian Li, Xiumei Li, Hui Hu
doi: 10.1016/j.virs.2022.01.025
Received: 26 May 2021 Accepted: 14 January 2022 Published: 24 January 2022
Abstract PDF ScienceDirect ESM
Porcine deltacoronavirus (PDCoV) is a novel discovered swine enteric coronavirus which can cause diarrhea and dehydration in pigs, particularly in neonatal piglets (Jung et al. 2016). At present, there are no commercial vaccines available for PDCoV. To control PDCoV transmission and perform antiviral therapy efficiently, a rapid and accurate diagnostic method to detect PDCoV is needed. PDCoV nucleocapsid (N) protein is the most abundant protein in the virus particle and plays essential roles in several stages of the viral lifecycle. It can produce high levels of antibodies at the early stage of PDCoV infection (Xu et al. 2013; Dinesh et al. 2020; Van Elslande et al. 2021). However, the characterization of epitopes on PDCoV N protein remains largely unknown.
Nano-bubble hydrogen water: An effective therapeutic agent against inflammation related disease caused by viral infection in zebrafish model
Chen Li, Yiran Cao, Fukuda Kohei, Haihong Hao, Guiqing Peng, Can Cheng, Jing Ye
doi: 10.1016/j.virs.2022.01.023
Received: 09 June 2021 Accepted: 08 October 2021 Published: 22 January 2022
Abstract PDF ScienceDirect ESM
Since the anti-inflammatory effect of hydrogen has been widely known, it was supposed that hydrogen could suppress tissue damage by inhibiting virus-related inflammatory reactions. However, hydrogen is slightly soluble in water, which leads to poor effect of oral hydrogen-rich water therapy. In this study, the nano-bubble hydrogen water (nano-HW) (about 0.7 ​ppm) was prepared and its therapeutic effect against viral infection was investigated by utilizing spring viraemia of carp virus (SVCV)-infected zebrafish as model. Three-month-old zebrafish were divided into nano-HW treatment–treated group and aquaculture water treated group (control group). The results revealed that the cumulative mortality rate of SVCV-infected zebrafish was reduced by 40% after treatment with nano-bubble hydrogen water, and qRT-PCR results showed that SVCV replication was significantly inhibited. Histopathological examination staining showed that SVCV infection caused tissue damage was greatly alleviated after treatment with nano-bubble hydrogen water. Futhermore, SVCV infection caused reactive oxygen species (ROS) accumulation was significantly reduced upon nano-HW treatment. The level of proinflammatory cytokines IL-1β, IL-8, and TNF-α was remarkably reduced in the nano-HW-treated group in vivo and in vitro. Taken together, our data demonstrated for the first time that nano-HW could inhibit the inflammatory response caused by viral infection in zebrafish, which suggests that nano-HW can be applied to antiviral research,and provides a novel therapeutic strategy for virus-caused inflammation related disease.
Molecular analysis of Coxsackievirus A24 variant isolates from three outbreaks of acute hemorrhagic conjunctivitis in 1988, 1994 and 2007 in Beijing, China
Junhan Li, Fang Huang, Yong Zhang, Tianjiao Ji, Shuangli Zhu, Dongyan Wang, Zhenzhi Han, Jinbo Xiao, Fenfen Si, Wenbo Xu, Dongmei Yan
doi: 10.1016/j.virs.2022.01.024
Received: 28 January 2021 Accepted: 14 January 2022 Published: 22 January 2022
Abstract PDF ScienceDirect ESM
Coxsackievirus A24 variant (CVA24v) is a major pathogen that causes continued outbreaks and pandemics of acute hemorrhagic conjunctivitis (AHC). In China, the first confirmed outbreak of CVA24v-related AHC occurred in Beijing in 1988, followed by another two significant outbreaks respectively in 1994 and 2007, which coincides with the three-stage dynamic distribution of AHC in the world after 1970s. To illustrate the genetic characteristics of CVA24v in different periods, a total of 23 strains were isolated from those three outbreaks and the whole genome of those isolations were sequenced and analyzed. Compared with the prototype strain, the 23 strains shared four nucleotide deletions in the 5′ UTR except the 0744 strain isolated in 2007. And at the 98th site, one nucleotide insertion was found in all the strains collected from 2007. From 1994 to 2007, amino acid polarity in the VP1 region at the 25th and the 32nd site were changed. Both the 3C and VP1 phylogenetic tree indicated that isolates from 1988 and 1994 belonged to Genotype III (GIII), and 2007 strains to Genotype IV (GIV). According to the Bayesian analysis based on complete genome sequence, the most recent common ancestors for the isolates in 1988, 1994 and 2007 were respectively estimated around October 1987, February 1993 and December 2004. The evolutionary rate of the CVA24v was estimated to be 7.45 ​× ​10−3 substitutions/site/year. Our study indicated that the early epidemic of CVA24v in Chinese mainland was the GIII. Point mutations and amino acid changes in different genotypes of CVA24v may generate intensity differences of the AHC outbreak. CVA24v has been evolving constantly with a relatively rapid rate.
Semen Extracellular Vesicles Mediate Vertical Transmission of Subgroup J Avian Leukosis Virus
Liqin Liao, Weiguo Chen, Xiangyu Zhang, Huanmin Zhang, Aijun Li, Yiming Yan, Zi Xie, Hongxing Li, Wencheng Lin, Jingyun Ma, Xinheng Zhang, Qingmei Xie
doi: 10.1016/j.virs.2022.01.026
Received: 16 June 2021 Accepted: 27 December 2021 Published: 22 January 2022
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Subgroup J avian leukosis virus (ALV-J) is a highly oncogenic retrovirus that has been devastating the global poultry industry since the late 1990s. The major infection model of ALV-J is vertical transmission, which is responsible for the congenital infection of progeny from generation to generation. Increasing evidence has suggested that extracellular vesicles (EVs) derived from virus-infected cells or biological fluids have been thought to be vehicles of transmission for viruses. However, the role of EVs in infection and transmission of ALV-J remains obscure. In the present study, semen extracellular vesicles (SE) were isolated and purified from ALV-J-infected rooster seminal plasma (SE-ALV-J), which was shown to contain ALV-J genomic RNA and partial viral proteins, as determined by RNA sequencing, reverse transcription-quantitative PCR and Western blotting. Furthermore, SE-ALV-J was proved to be able to transmit ALV-J infection to host cells and establish productive infection. More importantly, artificial insemination experiments showed that SE-ALV-J transmitted ALV-J infection to SPF hens, and subsequently mediated vertical transmission of ALV-J from the SPF hens to the progeny chicks. Taken together, the results of the present study suggested that ALV-J utilized host semen extracellular vesicles as a novel means for vertical transmission, enhancing our understanding on mechanisms underlying ALV-J transmission.
Identification of a novel hepacivirus in Mongolian gerbil (Meriones unguiculatus) from Shaanxi, China
Cui-hong An, Juan Li, Yi-ting Wang, Shou-min Nie, Wen-hui Chang, Hong Zhou, Lin Xu, Yang-xin Sun, Wei-feng Shi, Ci-xiu Li
doi: 10.1016/j.virs.2022.01.016
Received: 28 July 2021 Accepted: 10 October 2021 Published: 19 January 2022
Abstract PDF ScienceDirect
Hepaciviruses, members of the family Flaviviridae, are enveloped viruses containing a single-stranded positive-sense RNA genome of approximately 8.9–10.5 kb in size (Simmonds et al., 2017). To date, 15 species (Hepacivirus A–N, and P) have been documented within the Hepacivirus genus that show distinct host ranges, including primates, bats, horses, donkeys, cows, and various rodents (Hartlage et al., 2016). Seven rodent-associated hepaciviruses have been characterized, including hepacivirus E, I, G and H infecting rodents of Muridae, hepacivirus F and J infecting rodents of Cricetidae (de Souza et al., 2019), and heapcivirus P infecting rodents of Xerinae (Li et al., 2019). Additional unclassified rodent hapaciviruses have been described in diverse rodents from Dormouse, Echimyidae, Heteromyidae, and Spalacidae. Mongolian gerbils (Meriones unguiculatus) are small rodents belonging to the family Muridae and are widely distributed in the desert grasslands and steppes of northern China, Mongolia, and Russia (Liu et al., 2007). They have been reported as a major host of Yersinia pestis causing plagues in China in recent decades (Riehm et al., 2011). Moreover, Mongolian gerbil is known to be susceptible to various viruses and is a commonly used animal model for virus research (Li et al., 2009). Despite this, the natural virome of wild Meriones unguiculatus has not been described. Herein, we reported the first hepacivirus detected in Mongolian gerbils captured in Dingbian County of Shaanxi Province, one of the plague zones in China.
Analysis of severe human adenovirus infection outbreak in Guangdong Province, southern China in 2019
Wenkuan Liu, Shuyan Qiu, Li Zhang, Hongkai Wu, Xingui Tian, Xiao Li, Duo Xu, Jing Dai, Shujun Gu, Qian Liu, Dehui Chen, Rong Zhou
doi: 10.1016/j.virs.2022.01.010
Received: 07 July 2021 Accepted: 06 December 2021 Published: 17 January 2022
Abstract PDF ScienceDirect ESM
During 2018–2019, a severe human adenovirus (HAdV) infection outbreak occurred in southern China. Here, we screened 18 respiratory pathogens in 1,704 children (≤14 years old) hospitalized with acute respiratory illness in Guangzhou, China, in 2019. In total, 151 patients had positive HAdV test results; 34.4% (52/151) of them exhibited severe illness. HAdV infection occurred throughout the year, with a peak in summer. The median patient age was 3.0 (interquartile range: 1.1–5.0) years. Patients with severe HAdV infection exhibited increases in 12 clinical indexes (P ≤ 0.019) and decreases in four indexes (P ≤ 0.007), compared with patients exhibiting non-severe infection. No significant differences were found in age or sex distribution according to HAdV infection severity (P > 0.05); however, the distributions of comorbid disease and HAdV co-infection differed according to HAdV infection severity (P < 0.05). The main epidemic types were HAdV-3 (47.0%, 71/151) and HAdV-7 (46.4%, 70/151). However, the severe illness rate was significantly higher in patients with HAdV-7 (51.4%) than in patients with HAdV-3 (19.7%) and other types of HAdV (20%) (P < 0.001). Sequencing analysis of genomes/capsid genes of 13 HAdV-7 isolates revealed high similarity to previous Chinese isolates. A representative HAdV-7 isolate exhibited a similar proliferation curve to the curve described for the epidemic HAdV-3 strain Guangzhhou01 (accession no. DQ099432) (P > 0.05); the HAdV-7 isolate exhibited stronger virulence and infectivity, compared with HAdV-3 (P < 0.001). Overall, comorbid disease, HAdV co-infection, and high virulence and infectivity of HAdV-7 were critical risk factors for severe HAdV infection; these data can facilitate treatment, control, and prevention of HAdV infection.
Novel pegiviruses infecting wild birds and rodents
Wentao Zhu, Jing Yang, Shan Lu, Yuyuan Huang, Dong Jin, Ji Pu, Liyun Liu, Zhenjun Li, Mang Shi, Jianguo Xu
doi: 10.1016/j.virs.2022.01.013
Received: 30 August 2021 Accepted: 04 November 2021 Published: 17 January 2022
Abstract PDF ScienceDirect ESM
Pegivirus (family Flaviviridae) is a genus of small enveloped RNA viruses that mainly causes blood infections in various mammals including human. Herein, we carried out an extensive survey of pegiviruses from a wide range of wild animals mainly sampled in the Qinghai-Tibet Plateau of China. Three novel pegiviruses, namely Passer montanus pegivirus, Leucosticte brandti pegivirus and Montifringilla taczanowskii pegivirus, were identified from different wild birds, and one new rodent pegivirus, namely Phaiomys leucurus pegivirus, was identified from Blyth's vole. Interestingly, the pegiviruses of non-mammalian origin discovered in this study substantially broaden the host range of Pegivirus to avian species. Co-evolutionary analysis showed virus-host co-divergence over long evolutionary timescales, and indicated that pegiviruses largely followed a virus-host co-divergence relationship. Overall, this work extends the biodiversity of the Pegivirus genus to those infecting wild birds and hence revises the host range and evolutionary history of genus Pegivirus.
Immunogenicity of a recombinant VSV-Vectored SARS-CoV vaccine induced robust immunity in rhesus monkeys after single-dose immunization
Dan Shan, Xiaoyan Tang, Renqiang Liu, Dan Pan, Xijun Wang, Jinying Ge, Zhiyuan Wen, Zhigao Bu
doi: 10.1016/j.virs.2022.01.002
Received: 23 February 2021 Accepted: 04 August 2021 Published: 12 January 2022
Abstract PDF ScienceDirect ESM
Severe acute respiratory syndrome (SARS) is a highly contagious zoonotic disease caused by SARS coronavirus (SARS-CoV). Since its outbreak in Guangdong Province of China in 2002, SARS has caused 8096 infections and 774 deaths by December 31st, 2003. Although there have been no more SARS cases reported in human populations since 2004, the recent emergence of a novel coronavirus disease (COVID-19) indicates the potential of the recurrence of SARS and other coronavirus disease among humans. Thus, developing a rapid response SARS vaccine to provide protection for human populations is still needed. Spike (S) protein of SARS-CoV can induce neutralizing antibodies, which is a pivotal immunogenic antigen for vaccine development. Here we constructed a recombinant chimeric vesicular stomatitis virus (VSV) VSVΔG-SARS, in which the glycoprotein (G) gene is replaced with the SARS-CoV S gene. VSVΔG-SARS maintains the bullet-like shape of the native VSV, with the heterogeneous S protein incorporated into its surface instead of G protein. The results of safety trials revealed that VSVΔG-SARS is safe and effective in mice at a dose of 1 ​× ​106 TCID50. More importantly, only a single-dose immunization of 2 ​× ​107 TCID50 can provide high-level neutralizing antibodies and robust T cell responses to non-human primate animal models. Thus, our data indicate that VSVΔG-SARS can be used as a rapid response vaccine candidate. Our study on the recombinant VSV-vectored SARS-CoV vaccines can accumulate experience and provide a foundation for the new coronavirus disease in the future.

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Review
Updates on CRISPR-based gene editing in HIV-1/AIDS therapy
Zhihao Zhang, Wei Hou, Shuliang Chen
2022, 37(1): 1-10.  doi: 10.1016/j.virs.2022.01.017
Received: 31 July 2021 Accepted: 15 November 2021 Published: 19 January 2022
[PDF 1160KB] ScienceDirect
Although tremendous efforts have been made to prevent and treat HIV-1 infection, HIV-1/AIDS remains a major threat to global human health. The combination antiretroviral therapy (cART), although able to suppress HIV-1 replication, cannot eliminate the proviral DNA integrated into the human genome and thus requires lifelong treatment that may lead to various side effects. In recent years, clustered regularly interspaced short palindromic repeat (CRISPR)-associated nuclease 9 (Cas9) related gene-editing systems have been developed and designed as effective ways to treat HIV-1 infection. However, new gene-targeting tools derived from or functioning like CRISPR/Cas9, including base editor, prime editing, SHERLOCK, DETECTR, PAC-MAN, ABACAS, pfAGO, have been developed and optimized for pathogens detection and diseases correction. Here, we summarize recent studies on HIV-1/AIDS gene therapy and provide more gene-editing targets based on studies relating to the molecular mechanism of HIV-1 infection. We also identify the strategies and potential applications of these new gene-editing technologies for HIV-1/AIDS treatment in the future. Moreover, we discuss the caveats and problems that should be addressed before the clinical use of these versatile CRISPR-based gene targeting tools. Finally, we offer alternative solutions to improve the practice of gene targeting in HIV-1/AIDS gene therapy.
The diversity and evolution of retroviruses: Perspectives from viral “fossils”
Jialu Zheng, Yutong Wei, Guan-Zhu Han
2022, 37(1): 11-18.  doi: 10.1016/j.virs.2022.01.019
Received: 18 August 2021 Accepted: 12 October 2021 Published: 19 January 2022
[PDF 1781KB] ScienceDirect
Retroviruses exclusively infect vertebrates, causing a variety of diseases. The replication of retroviruses requires reverse transcription and integration into host genomes. When infecting germline cells, retroviruses become inherited vertically, forming endogenous retroviruses (ERVs). ERVs document past viral infections, providing molecular fossils for studying the evolutionary history of retroviruses. In this review, we summarize the recent advances in understanding the diversity and evolution of retroviruses from the perspectives of viral fossils, and discuss the effects of ERVs on the evolution of host biology.
Research Article
Seroepidemiologic study on convalescent sera from dengue fever patients in Jinghong, Yunnan
Yingshuo Ma, Man Li, Lyu Xie, Na Gao, Dongying Fan, Kaihao Feng, Yao Yao, Yong Zhou, Ziyang Sheng, Hongning Zhou, Hui Chen, Jing An
2022, 37(1): 19-29.  doi: 10.1016/j.virs.2021.12.001
Received: 29 April 2021 Accepted: 28 August 2021 Published: 17 December 2021
[PDF 1448KB] ScienceDirect ESM
After dengue virus (DENV) infection, antibody-dependent enhancement (ADE) is easy to occur when the neutralizing antibody (NAb) gradually decreases to a sub-neutralizing concentration. In this cohort surveillance, we utilized sera samples collected from dengue fever patients at different convalescent phases in Jinghong City, to investigate the dynamic change rule of DENV-specific antibodies, and to analyze the risk of ADE caused by secondary infection with heterologous serotypes DENVs. For baseline serosurvey, 191 four-year and 99 six-year sera samples during convalescence were collected in 2017 and 2019, respectively. The positive rate of DENV-specific immunoglobulin G was 98.4% in 2017, which significantly decreased to 82.8% in 2019. The geometric mean titer (GMT) of NAb decreased from 1:155.35 to 1:46.66. Among 290 overall samples, 73 paired consecutive samples were used for follow-up serosurvey. In four-year sera, the GMTs of NAb against DENV-3 and cross-reactive antibodies against DENV-1, DENV-2 and DENV-4 were 1:167.70, 1:13.80, 1:18.54 and 1:45.26, respectively, which decreased to 1:53.18, 1:10.30, 1:14.60 and 1:8.17 in six-year sera. In age-stratified analysis, due to the increasing number of ADE positive samples from 2017 to 2019 in 31–40 and 51–60 years groups, the risk of ADE in DENV-4 infection was positively associated with the extension of convalescent phase, and the odd ratio was higher than other groups. With the recovery period lengthened, the risk of secondary infection with DENV-1 and DENV-2 was reduced. Our results offer essential experimental data for risk prediction of severe dengue in hyper-endemic dengue areas, and provide crucial scientific insight for the development of effective dengue vaccines.
Characterization of two SARS-CoV-2 subgenomic RNA dynamics in severe COVID-19 patients
Xiaohui Zou, Shengrui Mu, Yeming Wang, Li Guo, Lili Ren, Xiaoyan Deng, Haibo Li, Jiankang Zhao, Yulin Zhang, Hui Li, Binghuai Lu, Chaolin Huang, Bin Cao
2022, 37(1): 30-37.  doi: 10.1016/j.virs.2022.01.008
Received: 28 April 2021 Accepted: 29 December 2021 Published: 17 January 2022
[PDF 898KB] ScienceDirect ESM
Little is known about Subgenomic RNA (sgRNA) dynamics in patients with Coronavirus diseases 2019 (COVID-19). We collected 147 throat swabs, 74 gut swabs and 46 plasma samples from 117 COVID-19 patients recruited in the LOTUS China trial (ChiCTR2000029308) and compared E and orf7a sgRNA load in patients with different illness duration, outcome, and comorbidities. Both sgRNAs were detected in all the three types of samples, with longest duration of 25, 13, and 17 days for E sgRNA, and 32, 28, and 17 days for orf7a sgRNA in throat, gut, and plasma, respectively. A total of 95% (57/60) of patients had no E sgRNA detected after 10 days post treatment, though 86% of them were still E RNA positive. High correlation on titer was observed between sgRNA encoding E and orf7a gene. sgRNA showed similar variation in the standard care and Lopinavir-Ritonavir group. Patients with diabetes and heart diseases showed higher pharyngeal E sgRNA at the first day (P = 0.016 and 0.013, respectively) but no difference at five days after treatment, compared with patients without such commodities. Patients with hypertension and cerebrovascular diseases showed no difference in the pharyngeal sgRNA levels at both one and five days after treatment, compared with patients without these two commodities. E sgRNA levels in the initial infection showed no correlation with the serum antibody against spike, nucleoprotein, and receptor binding domains at ten days later. sgRNA lasted a long period in COVID-19 patients and might have little effect on humoral response.
Combined insertion of basic and non-basic amino acids at hemagglutinin cleavage site of highly pathogenic H7N9 virus promotes replication and pathogenicity in chickens and mice
Aobaixue Zhou, Jiahao Zhang, Huanan Li, Qiang Xu, Yiqun Chen, Bo Li, Wanying Liu, Guanming Su, Xingxing Ren, Guangjie Lao, Baozheng Luo, Ming Liao, Wenbao Qi
2022, 37(1): 38-47.  doi: 10.1016/j.virs.2022.01.001
Received: 02 April 2021 Accepted: 22 July 2021 Published: 13 January 2022
[PDF 1734KB] ScienceDirect ESM
Since mid-2016, the low pathogenic H7N9 influenza virus has evolved into a highly pathogenic (HP) phenotype in China, raising many concerns about public health and poultry industry. The insertion of a “KRTA” motif at hemagglutinin cleavage site (HACS) occurred in the early stage of HP H7N9 variants. During the co-circulation, the HACS of HP-H7N9 variants were more polymorphic in birds and humans. Although HP-H7N9 variants, unlike the H5 subtype virus, exhibited the insertions of basic and non-basic amino acids, the underlying function of those insertions and substitutions remains unclear. The results of bioinformatics analysis indicated that the PEVPKRKRTAR/G motif of HACS had become the dominant motif in China. Then, we generated six H7N9 viruses bearing the PEIPKGR/G, PEVPKGR/G, PEVPKRKRTAR/G, PEVPKGKRTAR/G, PEVPKGKRIAR/G, and PEVPKRKRR/G motifs. Interestingly, after the deletion of threonine and alanine (TA) at HACS, the H7N9 viruses manifested decreased thermostability and virulence in mice, and the PEVPKRKRTAR/G-motif virus is prevalent in birds and humans probably due to its increased transmissibility and moderate virulence. By contrast, the insertion of non-basic amino acid isoleucine and alanine (IA) decreased the transmissibility in chickens and virulence in mice. Remarkably, the I335V substitution of H7N9 virus enhanced infectivity and transmission in chickens, suggesting that the combination of mutations and insertions of amino acids at the HACS promoted replication and pathogenicity in chickens and mice. The ongoing evolution of H7N9 increasingly threatens public health and poultry industry, so, its comprehensive surveillance and prevention of H7N9 viruses should be pursued.
Nucleolin interacts with the rabbit hemorrhagic disease virus replicase RdRp, nonstructural proteins p16 and p23, playing a role in virus replication
Jie Zhu, Qiuhong Miao, Hongyuan Guo, Aoxing Tang, Dandan Dong, Jingyu Tang, Fang Wang, Guangzhi Tong, Guangqing Liu
2022, 37(1): 48-59.  doi: 10.1016/j.virs.2022.01.004
Received: 23 June 2021 Accepted: 15 September 2021 Published: 12 January 2022
[PDF 2669KB] ScienceDirect ESM
Rabbit hemorrhagic disease virus (RHDV) is a member of the Caliciviridae family and cannot be propagated in vitro, which has impeded the progress of investigating its replication mechanism. Construction of an RHDV replicon system has recently provided a platform for exploring RHDV replication in host cells. Here, aided by this replicon system and using two-step affinity purification, we purified the RHDV replicase and identified its associated host factors. We identified rabbit nucleolin (NCL) as a physical link, which mediating the interaction between other RNA-dependent RNA polymerase (RdRp)-related host proteins and the viral replicase RdRp. We found that the overexpression or knockdown of NCL significantly increased or severely impaired RHDV replication in RK-13 cells, respectively. NCL was identified to directly interact with RHDV RdRp, p16, and p23. Furthermore, NCL knockdown severely impaired the binding of RdRp to RdRp-related host factors. Collectively, these results indicate that the host protein NCL is essential for RHDV replication and acts as a physical link between viral replicase and host proteins.
Metagenomic analysis of viral community in the Yangtze River expands known eukaryotic and prokaryotic virus diversity in freshwater
Juan Lu, Shixing Yang, Xiaodan Zhang, Xiangming Tang, Ju Zhang, Xiaochun Wang, Hao Wang, Quan Shen, Wen Zhang
2022, 37(1): 60-69.  doi: 10.1016/j.virs.2022.01.003
Received: 21 July 2021 Accepted: 03 September 2021 Published: 13 January 2022
[PDF 3711KB] ScienceDirect ESM
Viruses in aquatic ecosystems are characterized by extraordinary abundance and diversity. Thus far, there have been limited studies focused on viral communities in river water systems. Here, we investigated the virome of the Yangtze River Delta using viral metagenomic analysis. The compositions of viral communities from six sampling sites were analyzed and compared. By using library construction and next generation sequencing, contigs and singlet reads similar to viral sequences were classified into 17 viral families, including nine dsDNA viral families, four ssDNA viral families and four RNA viral families. Statistical analysis using Friedman test suggested that there was no significant difference among the six sampling sites (P > 0.05). The viromes in this study were all dominated by the order Caudovirales, and a group of Freshwater phage uvFW species were particularly prevalent among all the samples. The virome from Nanjing presented a unique pattern of viral community composition with a relatively high abundance of family Parvoviridae. Phylogenetic analyses based on virus hallmark genes showed that the Caudovirales order and CRESS-DNA viruses presented high genetic diversity, while viruses in the Microviridae and Parvoviridae families and the Riboviria realm were relatively conservative. Our study provides the first insight into viral community composition in large river ecosystem, revealing the diversity and stability of river water virome, contributing to the proper utilization of freshwater resource.
Genome-wide transcriptome analysis of porcine epidemic diarrhea virus virulent or avirulent strain-infected porcine small intestinal epithelial cells
Ouyang Peng, Xiaona Wei, Usama Ashraf, Fangyu Hu, Yongbo Xia, Qiuping Xu, Guangli Hu, Chunyi Xue, Yongchang Cao, Hao Zhang
2022, 37(1): 70-81.  doi: 10.1016/j.virs.2022.01.011
Received: 28 July 2021 Accepted: 07 January 2022 Published: 18 January 2022
[PDF 4244KB] ScienceDirect ESM
Porcine epidemic diarrhea virus (PEDV) is the main cause of diarrhea, vomiting, and mortality in pigs, which results in devastating economic loss to the pig industry around the globe. In recent years, the advent of RNA-sequencing technologies has led to delineate host responses at late stages of PEDV infection; however, the comparative analysis of host responses to early-stage infection of virulent and avirulent PEDV strains is currently unknown. Here, using the BGI DNBSEQ RNA-sequencing, we performed global gene expression profiles of pig intestinal epithelial cells infected with virulent (GDS01) or avirulent (HX) PEDV strains for 3, 6, and 12 h. It was observed that over half of all significantly dysregulated genes in both infection groups exhibited a down-regulated expression pattern. Functional enrichment analyses indicated that the differentially expressed genes (DEGs) in the GDS01 group were predominantly related to autophagy and apoptosis, whereas the genes showing the differential expression in the HX group were strongly enriched in immune responses/inflammation. Among the DEGs, the functional association of TLR3 and IFIT2 genes with the HX and GDS01 strains replication was experimentally validated by TLR3 inhibition and IFIT2 overexpression systems in cultured cells. TLR3 expression was found to inhibit HX strain, but not GDS01 strain, replication by enhancing the IFIT2 expression in infected cells. In conclusion, our study highlights similarities and differences in gene expression patterns and cellular processes/pathways altered at the early-stage infection of PEDV virulent and avirulent strains. These findings may provide a foundation for establishing novel therapies to control PEDV infection.
Viral metagenomics reveals diverse viruses in the fecal samples of children with diarrhea
Shixing Yang, Yumin He, Ju Zhang, Dianqi Zhang, Yan Wang, Xiang Lu, Xiaochun Wang, Quan Shen, Likai Ji, Hongyan Lu, Wen Zhang
2022, 37(1): 82-93.  doi: 10.1016/j.virs.2022.01.012
Received: 09 August 2020 Accepted: 06 December 2021 Published: 17 January 2022
[PDF 4267KB] ScienceDirect ESM
Diarrhea is the third leading cause of death in developing countries in children under the age of five. About half a million children die of diarrhea every year, most of which in developing countries. Viruses are the main pathogen of diarrhea. In China, the fecal virome of children with diarrhea has been rarely studied. Using an unbiased viral metagenomics approach, we analyzed the fecal virome in children with diarrhea. Many DNA or RNA viruses associated with diarrhea identified in those fecal samples were mainly from six families of Adenoviridae, Astroviridae, Caliciviridae, Parvoviridae, Picornaviridae, and Reoviridae. Among them, the family of Caliciviridae accounts for the largest proportion of 78.42%, following with Adenoviridae (8.94%) and Picornaviridae (8.36%). In addition to those diarrhea-related viruses that have already been confirmed to cause human diarrhea, the viruses not associated with diarrhea were also identified including anellovirus and picobirnavirus. This study increased our understanding of diarrheic children fecal virome and provided valuable information for the prevention and treatment of viral diarrhea in this area.
Screening of novel synthetic derivatives of dehydroepiandrosterone for antivirals against flaviviruses infections
Muhammad Imran, Luping Zhang, Bohan Zheng, Zikai Zhao, Dengyuan Zhou, Shengfeng Wan, Zheng Chen, Hongyu Duan, Qiuyan Li, Xueqin Liu, Shengbo Cao, Shaoyong Ke, Jing Ye
2022, 37(1): 94-106.  doi: 10.1016/j.virs.2022.01.007
Received: 15 March 2021 Accepted: 12 October 2021 Published: 18 January 2022
[PDF 6720KB] ScienceDirect
Flaviviruses are important arthropod-borne pathogens that represent an immense global health problem. Their unprecedented epidemic rate and unpredictable clinical features underscore an urgent need for antiviral interventions. Dehydroepiandrosterone (DHEA) is a natural occurring adrenal-derived steroid in the human body that has been associated in protection against various infections. In the present study, the plaque assay based primary screening was conducted on 32 synthetic derivatives of DHEA against Japanese encephalitis virus (JEV) to identify potent anti-flaviviral compounds. Based on primary screening, HAAS-AV3026 and HAAS-AV3027 were selected as hits from DHEA derivatives that exhibited strong antiviral activity against JEV (IC50 = 2.13 and 1.98 μmol/L, respectively) and Zika virus (ZIKV) (IC50 = 3.73 and 3.42 μmol/L, respectively). Mechanism study indicates that HAAS-AV3026 and HAAS-AV3027 do not exhibit inhibitory effect on flavivirus binding and entry process, while significantly inhibit flavivirus infection at the replication stage. Moreover, indirect immunofluorescence assay, Western blot analyses, and quantitative reverse transcription-PCR (qRT-PCR) revealed a potent antiviral activity of DHEA derivatives hits against JEV and ZIKV in terms of inhibition of viral infection, protein production, and viral RNA synthesis in Vero cells. Taken together, our results may provide a basis for the development of new antivirals against flaviviruses.
A new luciferase immunoprecipitation system assay provided serological evidence for missed diagnosis of severe fever with thrombocytopenia syndrome
Shengyao Chen, Minjun Xu, Xiaoli Wu, Yuan Bai, Junming Shi, Min Zhou, Qiaoli Wu, Shuang Tang, Fei Deng, Bo Qin, Shu Shen
2022, 37(1): 107-114.  doi: 10.1016/j.virs.2022.01.018
Received: 11 August 2021 Accepted: 12 October 2021 Published: 20 January 2022
[PDF 786KB] ScienceDirect ESM
Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV) infection, was first reported in 2010 in China with an initial fatality of up to 30%. The laboratory confirmation of SFTSV infection in terms of detection of viral RNA or antibody levels is critical for SFTS diagnosis and therapy. In this study, a new luciferase immunoprecipitation system (LIPS) assay based on pREN2 plasmid expressing SFTSV NP gene and tagged with Renilla luciferase (Rluc), was established and used to investigate the levels of antibody responses to SFTSV. Totally 464 serum samples from febrile patients were collected in the hospital of Shaoxing City in Zhejiang Province in 2019. The results showed that 82 of the 464 patients (17.7%) had antibody response to SFTSV, which were further supported by immunofluorescence assays (IFAs). Further, qRT-PCR and microneutralization tests showed that among the 82 positive cases, 15 patients had viremia, 10 patients had neutralizing antibody, and one had both (totally 26 patient). However, none of these patients were diagnosed as SFTS in the hospital probably because of their mild symptoms or subclinical manifestations. All the results indicated that at least the 26 patients having viremia or neutralizing antibody were the missed diagnosis of SFTS cases. The findings suggested the occurrence of SFTS and the SFTS incidence were higher than the reported level in Shaoxing in 2019, and that LIPS may provide an alternative strategy to confirm SFTSV infection in the laboratory.
A single nonsynonymous mutation on ZIKV E protein-coding sequences leads to markedly increased neurovirulence in vivo
Zhihua Liu, Yawei Zhang, Mengli Cheng, Ningning Ge, Jiayi Shu, Zhiheng Xu, Xiao Su, Zhihua Kou, Yigang Tong, Chengfeng Qin, Xia Jin
2022, 37(1): 115-126.  doi: 10.1016/j.virs.2022.01.021
Received: 09 September 2021 Accepted: 20 October 2021 Published: 21 January 2022
[PDF 3408KB] ScienceDirect ESM
Zika virus (ZIKV) can infect a wide range of tissues including the developmental brain of human fetus. Whether specific viral genetic variants are linked to neuropathology is incompletely understood. To address this, we have intracranially serially passaged a clinical ZIKV isolate (SW01) in neonatal mice and discovered variants that exhibit markedly increased virulence and neurotropism. Deep sequencing analysis combining with molecular virology studies revealed that a single 67D (Aspartic acid) to N (Asparagine) substitution on E protein is sufficient to confer the increased virulence and neurotropism in vivo. Notably, virus clones with D67N mutation had higher viral production and caused more severe cytopathic effect (CPE) in human neural astrocytes U251 cells in vitro, indicating its potential neurological toxicity to human brain. These findings revealed that a single mutation D67N on ZIKV envelope may lead to severe neuro lesion that may help to explain the neurovirulence of ZIKV and suggest monitoring the occurrence of this mutation during nature infection may be important.
Cryo-EM structure of glycoprotein C from Crimean-Congo hemorrhagic fever virus
Na Li, Guibo Rao, Zhiqiang Li, Jiayi Yin, Tingting Chong, Kexing Tian, Yan Fu, Sheng Cao
2022, 37(1): 127-137.  doi: 10.1016/j.virs.2022.01.015
Received: 25 October 2021 Accepted: 12 November 2021 Published: 18 January 2022
[PDF 4966KB] ScienceDirect ESM
Crimean-Congo hemorrhagic fever virus (CCHFV) is a causative agent of serious hemorrhagic diseases in humans with high mortality rates. CCHFV glycoprotein Gc plays critical roles in mediating virus-host membrane fusion and has been studied extensively as an immunogen. However, the molecular mechanisms involved in membrane fusion and Gc-specific antibody-antigen interactions remain unresolved largely because structural information of this glycoprotein is missing. We designed a trimeric protein including most of the ectodomain region of Gc from the prototype CCHFV strain, IbAr10200, which enabled the cryo-electron microscopy structure to be solved at a resolution of 2.8 Å. The structure confirms that CCHFV Gc is a class II fusion protein. Unexpectedly, structural comparisons with other solved Gc trimers in the postfusion conformation revealed that CCHFV Gc adopted hybrid architectural features of the fusion loops from hantaviruses and domain III from phenuiviruses, suggesting a complex evolutionary pathway among these bunyaviruses. Antigenic sites on CCHFV Gc that protective neutralizing antibodies target were mapped onto the CCHFV Gc structure, providing valuable information that improved our understanding of potential neutralization mechanisms of various antibodies.
Letter
An integrated rapid nucleic acid detection assay based on recombinant polymerase amplification for SARS-CoV-2
Ying Tang, Yiqin Wang, Yuchang Li, Huai Zhao, Sen Zhang, Ying Zhang, Jing Li, Yuehong Chen, Xiaoyan Wu, Chengfeng Qin, Tao Jiang, Xiaoping Kang
2022, 37(1): 138-141.  doi: 10.1016/j.virs.2022.01.006
Received: 31 May 2021 Accepted: 30 September 2021 Published: 13 January 2022
[PDF 883KB] ScienceDirect ESM
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that causes the outbreak of coronavirus disease 2019 (COVID-19) (Li et al., 2020a). Viral nucleic acid testing is the standard method for the laboratory diagnosis of COVID-19 (Wu et al., 2020a; Zhu et al., 2020). Currently, a variety of qPCR-based detection kits are used for laboratory-based detection and confirmation of SARS-CoV-2 infection (Corman et al., 2020; Hussein et al., 2020; Ruhan et al., 2020; Veyer et al., 2020). Conventional qPCR involves virus inactivation, nucleic acid extraction, and qPCR amplification procedures. Therefore, the process is complicated, which usually takes longer than 2 h, and requires biosafety laboratories and professional staff. Thus, qPCR is not suitable for use in field or medical units. To reduce the operation steps, automatic integrated qPCR detection systems that combine nucleic acid extraction and qPCR amplification in a sealed cartridge were developed to detect viruses in clinical samples (Li et al., 2020b). However, the detection time is still longer than 1 h. Therefore, rapid nucleic acid detection systems are needed to further improve the detection efficiency.
Fish ACE2 is not susceptible to SARS-CoV-2
Shi-Zhe Xie, Mei-Qin Liu, Ren-Di Jiang, Hao-Feng Lin, Wei Zhang, Bei Li, Jia Su, Fei Ke, Qi-Ya Zhang, Zheng-Li Shi, Xing-Lou Yang
2022, 37(1): 142-144.  doi: 10.1016/j.virs.2022.01.020
Received: 26 August 2021 Accepted: 12 January 2022 Published: 20 January 2022
[PDF 883KB] ScienceDirect ESM
The ongoing pandemic of coronavirus disease 2019 (COVID-19) has reshaped our daily life and caused > 4 million deaths worldwide (https://covid19.who.int/). Although lockdown and vaccination have improved the situation in many countries, imported cases and sporadic outbreaks pose a constant stress to the prevention and control of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent responsible for COVID-19, has a positive-sense single-stranded RNA genome of 30 kb (Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, 2020). We and other groups have demonstrated that the SARS-CoV-2 could use the angiotensin-converting enzyme 2 (ACE2) as cell receptor, including orthologs of a broad range of animal species such as human, bats, ferrets, pigs, cats, and dogs (Hoffmann et al., 2020; Zhou et al., 2020; Liu et al., 2021). Although the evolutionary origin of SARS-CoV-2 can be linked to the discoveries of diverse coronaviruses related to SARS-CoV-2 in wild animals such as bats (Zhou et al., 2020; Wacharapluesadee et al., 2021) and pangolins (Liu et al., 2019; Lam et al., 2020), the direct origin of SARS-CoV-2 in humans remains unknown. In China, several sporadic outbreaks of COVID-19 in 2020 were linked to food in cold chain sold at trade markets, including salmon meat (http://www.nhc.gov.cn/xcs/yqtb/list_gzbd.shtml) (Yang et al., 2020). The detection of SARS-CoV-2 RNA on the surface of frozen meat for as long as 20 days has also been reported (Feng et al., 2021). A concern regarding the potential role of fish in SARS-CoV-2 transmission has also been raised. Therefore, we investigated the susceptibility of fish ACE2 to SARS-CoV-2.
Tilorone confers robust in vitro and in vivo antiviral effects against severe fever with thrombocytopenia syndrome virus
Jingjing Yang, Yunzheng Yan, Qingsong Dai, Jiye Yin, Lei Zhao, Yuexiang Li, Wei Li, Wu Zhong, Ruiyuan Cao, Song Li
2022, 37(1): 145-148.  doi: 10.1016/j.virs.2022.01.014
Received: 08 September 2021 Accepted: 25 November 2021 Published: 18 January 2022
[PDF 1392KB] ScienceDirect ESM
Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging pathogen, is a tick-borne bunyavirus belonging to the genus Bandavirus in the family Phenuiviridae (Kuhn et al., 2020). This pathogen was first identified in China during the heightened surveillance of acute febrile illness in 2009, and has been reported to cause several outbreaks in eastern Asia areas, including China, Japan, and Korea (Yu et al., 2011). Besides, Vietnam has also reported several confirmed SFTS cases (Tran et al., 2019). The mortality rate in hospitalised patients with SFTSV infection is up to 10%–30%. Moreover, SFTSV has been reported to possibly transmitted by the contact of body fluids from person-to-person, and extensive SFTSV contamination was detected in the patient rooms (Kim et al., 2015). These reports suggest that more stringent isolation measures are needed for the prevention of massive SFTSV outbreak.
Epidemiological evidence of mosquito-borne viruses among persons and vectors in Iran: A study from North to South
Abbas Ahmadi Vasmehjani, Farhad Rezaei, Mohammad Farahmand, Talat Mokhtari-Azad, Mohammad Reza Yaghoobi-Ershadi, Mohsen Keshavarz, Hamid Reza Baseri, Morteza Zaim, Mahmood Iranpour, Habibollah Turki, Mohammad Esmaeilpour-Bandboni
2022, 37(1): 149-152.  doi: 10.1016/j.virs.2022.01.005
Received: 12 July 2020 Accepted: 09 August 2021 Published: 13 January 2022
[PDF 717KB] ScienceDirect ESM
Arthropod-borne viruses are a group of the most important emerging pathogens. They cause a range of diseases in vertebrate hosts and threaten human health (Gan and Leo, 2014). The global distribution of arboviruses is associated with the vector which is strongly affected by changes in environmental conditions. Dengue virus (DENV) and Chikungunya virus (CHIKV), which cause high annual infected cases and have an increasing geographic distribution, are transmitted by Aedes spp. mosquitoes, in particular Ae. albopictus and Ae. Aegypti (Presti et al., 2014; Higuera and Ramírez, 2018). Although, the main vector of dengue virus, Ae. aegypti, was not detected in Iran, other possible important vectors such as Ae. Albopictus and Ae. unilineatus were recorded (Doosti et al., 2016; Yaghoobi-Ershadi et al., 2017). West Nile virus (WNV), a member of the genus Flaviviruses, is one of the most widespread arboviruses (Chancey et al., 2015). The epidemiological evidence of WNV in different hosts in Iran was found (Bagheri et al., 2015), and the circulation of WNV in the main vector, Culex pipiens s.l. and Cx. pipiens, has been proved (Shahhosseini et al., 2017). Due to limited information on the situation of CHIKV, DENV and WNV in Iran, we performed a wide geographical investigation to determine the prevalence of IgG specific antibodies in human samples as well as the genome of WNV, CHIKV and DENV in mosquitoes.
Perspective
Footprints of SARS-CoV-2 genome diversity in Pakistan, 2020–2021
Zaira Rehman, Massab Umair, Aamer Ikram, Ammad Fahim, Muhammad Salman
2022, 37(1): 153-155.  doi: 10.1016/j.virs.2022.01.009
Received: 25 October 2021 Accepted: 10 January 2022 Published: 11 February 2022
[PDF 775KB] ScienceDirect
The rapid spread of SARS-CoV-2 has significantly impacted the worldwide health system. The SARS-CoV-2 currently bears a remarkably low genetic diversity even though it carries one of the largest RNA genomes among viruses (Rausch et al., 2020). However, the coronaviruses harbor the capability of undergoing recombination at a high rate which can lead to the emergence of novel viral derivatives (Rausch et al., 2020; Gribble et al., 2021). This in turn requires not only global surveillance of SARS-CoV-2 genome in various countries but also careful scrutiny in animal genomic reservoirs. Conventionally, RNA viruses evolve with a high mutation rate, however, the presence of ExoN ribonuclease in SARS-CoV-2 genome has made its case different from other viral species (Gribble et al., 2021). The variables of natural selection which potentially drift the SARS-CoV-2 evolutionary dynamics can be recorded by analyzing deposited sequence genomes for its fitness, transmissibility potential, and pathogenicity (Rouchka et al., 2020). This can potentially provide a way to draw a holistic picture at a national level, while simultaneously providing a comparative overview with worldwide sequences.