For best viewing of the website please use Mozilla Firefox or Google Chrome.

Just Accepted

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).

Display Method:         

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
Received: 25 October 2021 Accepted: 12 November 2020 Published: 26 November 2021
[Abstract] Springerlink
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 adopts 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.
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
Received: 11 August 2021 Accepted: 12 October 2021 Published: 26 November 2021
[Abstract] Springerlink
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.
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
Received: 08 September 2021 Accepted: 25 November 2021 Published: 25 November 2021
[Abstract] Springerlink
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.
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
Received: 09 September 2021 Accepted: 20 October 2021 Published: 17 November 2021
[Abstract] [PDF 2248KB] Springerlink
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 maybe important.
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
Received: 09 June 2021 Accepted: 08 October 2021 Published: 16 November 2021
[Abstract] Springerlink
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. H&E 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.
Updates on CRISPR-based gene editing in HIV-1/AIDS therapy
Zhihao Zhang, Wei Hou, Shuliang Chen
Received: 11 August 2021 Accepted: 10 November 2021 Published: 15 November 2021
[Abstract] [PDF 610KB] Springerlink
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.
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
Received: 28 July 2021 Accepted: 10 October 2021 Published: 05 November 2021
[Abstract] Springerlink
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.
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
Received: 30 August 2021 Accepted: 04 November 2021 Published: 04 November 2021
[Abstract] Springerlink
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.
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
Received: 12 July 2020 Accepted: 09 August 2021 Published: 22 October 2021
[Abstract] [PDF 789KB] Springerlink
The diversity and evolution of retroviruses: perspectives from viral “fossils”
Jialu Zheng, Yutong Wei, Guan-Zhu Han
Received: 18 August 2021 Accepted: 12 October 2021 Published: 22 October 2021
[Abstract] Springerlink
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.
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
Received: 23 June 2021 Accepted: 15 September 2021 Published: 19 October 2021
[Abstract] [PDF 1809KB] Springerlink

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 twostep 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.

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
Received: 03 June 2020 Accepted: 16 June 2020 Published: 19 October 2021
[Abstract] [PDF 1338KB] Springerlink
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
Received: 21 July 2021 Accepted: 03 September 2021 Published: 14 October 2021
[Abstract] [PDF 1205KB] Springerlink

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 provided 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.

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
Received: 23 February 2021 Accepted: 04 August 2021 Published: 08 October 2021
[Abstract] [PDF 1476KB] Springerlink 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 31th 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) VSVƤG-SARS, in which the glycoprotein (G) gene is replaced with the SARS-CoV S gene. VSVƤG-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 VSVƤG-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 VSVƤG-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.

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
Received: 29 April 2021 Accepted: 28 August 2021 Published: 29 September 2021
[Abstract] [PDF 604KB] Springerlink

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 DENV3 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.

Clinical Characteristics of Human Adenovirus Plastic Bronchitis in 10 Pediatric Cases: A Retrospective Study of Seven Years
Lingjian Zeng, Jianhua Wei, Yuyi Tang, Enmei Liu, Qubei Li, Na Zang
doi: 10.1007/s12250-021-00394-8
Received: 02 November 2020 Accepted: 25 April 2021 Published: 22 June 2021
[FullText HTML] [PDF 358KB] Springerlink