2024 Vol.39(3)

Foot-and-mouth disease (FMD) is a highly contagious disease caused by the FMD virus (FMDV). Although the cell receptor for FMDV has been identified, the specific mechanism of FMDV internalization after infection remains unknown. In this issue, Zhang et al. demonstrate that kinesin family member 5B (KIF5B) plays a crucial role in FMDV internalization. KIF5B directly interacts with VP1 to facilitate FMDV internalization by regulating clathrin uncoating. Further evidence indicates that KIF5B also facilitates the transport of viral particles to early and late endosomes during the early stages of FMDV infection. The cover image depicts FMDV (red) ‘hijacking’ host cell protein KIF5B (yellow) to invade the host cell and is then transported by KIF5B to the endosomes for uncoating, releasing RNA for reproduction. Subsequently, FMDV wrests cell resources (blue) within the host cell to complete its own replication, assembly, and release processes, thus completing its life cycle (Kindly provided by Dr. Wei Zhang and Prof. Haixue Zheng). See page 378-389 for details.

News and Views

Joint deletion of multifunctional MGF505-7R and H240R genes generates a safe and effective African swine fever virus attenuated live vaccine candidate

Changjiang Weng, Li Huang, Guangqiang Ye

2024, 39(3): 355 doi: 10.1016/j.virs.2024.04.007

Received: 11 December 2023 Accepted: 11 April 2024
Abstract [PDF 638 KB] ScienceDirect
Highlights
1. MGF505-7R and H240R are virulence-related genes.
2. ASFV-ΔMGF505-7R-ΔH240R is attenuated.
3. The candidate vaccine is safe and protective.
Research Articles

Evolutionary dynamics and comparative pathogenicity of clade 2.3.4.4b H5 subtype avian influenza viruses, China, 2021-2022

Siru Lin, Junhong Chen, Ke Li, Yang Liu, Siyuan Fu, Shumin Xie, Aimin Zha, Aiguo Xin, Xinyu Han, Yuting Shi, Lingyu Xu, Ming Liao, Weixin Jia

2024, 39(3): 358 doi: 10.1016/j.virs.2024.04.004

Received: 26 September 2023 Accepted: 18 April 2024
Abstract [PDF 2414 KB] ScienceDirectESM
The recent concurrent emergence of H5N1, H5N6, and H5N8 avian influenza viruses (AIVs) has led to significant avian mortality globally. Since 2020, frequent human-animal interactions have been documented. To gain insight into the novel H5 subtype AIVs (i.e., H5N1, H5N6 and H5N8), we collected 6102 samples from various regions of China between January 2021 and September 2022, and identified 41 H5Nx strains. Comparative analyses on the evolution and biological properties of these isolates were conducted. Phylogenetic analysis revealed that the 41 H5Nx strains belonged to clade 2.3.4.4b, with 13 related to H5N1, 19 to H5N6, and 9 to H5N8. Analysis based on global 2.3.4.4b viruses showed that all the viruses described in this study were likely originated from H5N8, exhibiting a heterogeneous evolutionary history between H5N1 and H5N6 during 2015-2022 worldwide. H5N1 showed a higher rate of evolution in 2021-2022 and more sites under positive selection pressure in 2015-2022. The antigenic profiles of the novel H5N1 and H5N6 exhibited notable variations. Further hemagglutination inhibition assay suggested that some A(H5N1) viruses may be antigenically distinct from the circulating H5N6 and H5N8 strains. Mammalian challenge assays demonstrated that the H5N8 virus (21GD001_H5N8) displayed the highest pathogenicity in mice, followed by the H5N1 virus (B1557_H5N1) and then the H5N6 virus (220086_H5N6), suggesting a heterogeneous virulence profile of H5 AIVs in the mammalian hosts. Based on the above results, we speculate that A(H5N1) viruses have a higher risk of emergence in the future. Collectively, these findings unveil a new landscape of different evolutionary history and biological characteristics of novel H5 AIVs in clade 2.3.4.4b, contributing to a better understanding of designing more effective strategies for the prevention and control of novel H5 AIVs.

Risk of infection with arboviruses in a healthy population in Pakistan based on seroprevalence

Shengyao Chen, Muhammad Saqib, Hafiz Sajid Khan, Yuan Bai, Usman Ali Ashfaq, Muhammad Khalid Mansoor, Abulimti Moming, Jing Liu, Min Zhou, Saifullah Khan Niazi, Qiaoli Wu, Awais-Ur-Rahman Sial, Shuang Tang, Muhammad Hassan Sarfraz, Aneela Javed, Sumreen Hayat, Mohsin Khurshid, Iahtasham Khan, Muhammad Ammar Athar, Zeeshan Taj, Bo Zhang, Fei Deng, Ali Zohaib, Shu Shen

2024, 39(3): 369 doi: 10.1016/j.virs.2024.04.001

Received: 19 November 2023 Accepted: 01 April 2024
Abstract [PDF 2172 KB] ScienceDirectESM
Infectious diseases caused by arboviruses are a public health concern in Pakistan. However, studies on data prevalence and threats posed by arboviruses are limited. This study investigated the seroprevalence of arboviruses in a healthy population in Pakistan, including severe fever with thrombocytopenia syndrome virus (SFTSV), Crimean-Congo hemorrhagic fever virus (CCHFV), Tamdy virus (TAMV), and Karshi virus (KSIV) based on a newly established luciferase immunoprecipitation system (LIPS) assays, and Zika virus (ZIKV) by enzyme-linked immunosorbent assays (ELISA). Neutralizing activities against these arboviruses were further examined from the antibody positive samples. The results showed that the seroprevalence of SFTSV, CCHFV, TAMV, KSIV, and ZIKV was 17.37%, 7.58%, 4.41%, 1.10%, and 6.48%, respectively, and neutralizing to SFTSV (1.79%), CCHFV (2.62%), and ZIKV (0.69%) were identified, as well as to the SFTSV-related Guertu virus (GTV, 0.83%). Risk factors associated with the incidence of exposure and levels of antibody response were analyzed. Moreover, co-exposure to different arboviruses was demonstrated, as thirty-seven individuals were having antibodies against multiple viruses and thirteen showed neutralizing activity. Males, individuals aged ≤40 years, and outdoor workers had a high risk of exposure to arboviruses. All these results reveal the substantial risks of infection with arboviruses in Pakistan, and indicate the threat from co-exposure to multiple arboviruses. The findings raise the need for further epidemiologic investigation in expanded regions and populations and the necessity to improve health surveillance in Pakistan.

KIF5B-mediated internalization of FMDV promotes virus infection

Wei Zhang, Fan Yang, Yang Yang, Weijun Cao, Wenhua Shao, Jiali Wang, Mengyao Huang, Zhitong Chen, Xiaoyi Zhao, Weiwei Li, Zixiang Zhu, Haixue Zheng

2024, 39(3): 378 doi: 10.1016/j.virs.2024.03.005

Received: 21 September 2023 Accepted: 13 March 2024
Abstract [PDF 3976 KB] ScienceDirectESM
Foot-and-mouth disease (FMD) is a highly contagious and economically important disease, which is caused by the FMD virus (FMDV). Although the cell receptor for FMDV has been identified, the specific mechanism of FMDV internalization after infection remains unknown. In this study, we found that kinesin family member 5B (KIF5B) plays a vital role during FMDV internalization. Moreover, we confirmed the interaction between KIF5B and FMDV structural protein VP1 by co-immunoprecipitation (Co-IP) and co-localization in FMDV-infected cells. In particular, the stalk [amino acids (aa) 413-678] domain of KIF5B was indispensable for KIF5B-VP1 interaction. Moreover, overexpression of KIF5B dramatically enhanced FMDV replication; consistently, knockdown or knockout of KIF5B suppressed FMDV replication. Furthermore, we also demonstrated that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating. KIF5B also promotes the transmission of viral particles to early and late endosomes during the early stages of infection. In conclusion, our results demonstrate that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating and intracellular transport. This study may provide a new therapeutic target for developing FMDV antiviral drugs.

Crucial role played by CK8+ cells in mediating alveolar injury remodeling for patients with COVID-19

Yufeng Li, Hengrui Hu, Jia Liu, Longda Ma, Xi Wang, Liang Liu, Qian Liu, Liang Ren, Jiang Li, Fei Deng, Zhihong Hu, Yiwu Zhou, Manli Wang

2024, 39(3): 390 doi: 10.1016/j.virs.2024.03.007

Received: 01 December 2023 Accepted: 18 March 2024
Abstract [PDF 8528 KB] ScienceDirectESM
The high risk of SARS-CoV-2 infection and reinfection and the occurrence of post-acute pulmonary sequelae have highlighted the importance of understanding the mechanism underlying lung repair after injury. To address this concern, comparative and systematic analyses of SARS-CoV-2 infection in COVID-19 patients and animals were conducted. In the lungs of nine patients who died of COVID-19 and one recovered from COVID-19 but died of unrelated disease in early 2020, damage-related transient progenitor (DATP) cells expressing CK8 marker proliferated significantly. These CK8+ DATP cells were derived from bronchial CK5+ basal cells. However, they showed different cell fate toward differentiation into type I alveolar cells in the deceased and convalescent patients, respectively. By using a self-limiting hamster infection model mimicking the dynamic process of lung injury remodeling in mild COVID-19 patients, the accumulation and regression of CK8+ cell marker were found to be closely associated with the disease course. Finally, we examined the autopsied lungs of two patients who died of infection by the recent Omicron variant and found that they only exhibited mild pathological injury with no CK8+ cell proliferation. These results indicate a clear pulmonary cell remodeling route and suggest that CK8+ DATP cells play a primary role in mediating alveolar remodeling, highlighting their potential applications as diagnostic markers and therapeutic targets.

Pseudorabies virus manipulates mitochondrial tryptophanyl-tRNA synthetase 2 for viral replication

Xiu-Qing Li, Meng-Pan Cai, Ming-Yang Wang, Bo-Wen Shi, Guo-Yu Yang, Jiang Wang, Bei-Bei Chu, Sheng-Li Ming

2024, 39(3): 403 doi: 10.1016/j.virs.2024.04.003

Received: 10 October 2023 Accepted: 11 April 2024
Abstract [PDF 2990 KB] ScienceDirectESM
The pseudorabies virus (PRV) is identified as a double-helical DNA virus responsible for causing Aujeszky's disease, which results in considerable economic impacts globally. The enzyme tryptophanyl-tRNA synthetase 2 (WARS2), a mitochondrial protein involved in protein synthesis, is recognized for its broad expression and vital role in the translation process. The findings of our study showed an increase in both mRNA and protein levels of WARS2 following PRV infection in both cell cultures and animal models. Suppressing WARS2 expression via RNA interference in PK-15 cells led to a reduction in PRV infection rates, whereas enhancing WARS2 expression resulted in increased infection rates. Furthermore, the activation of WARS2 in response to PRV was found to be reliant on the cGAS/STING/TBK1/IRF3 signaling pathway and the interferon-alpha receptor-1, highlighting its regulation via the type I interferon signaling pathway. Further analysis revealed that reducing WARS2 levels hindered PRV's ability to promote protein and lipid synthesis. Our research provides novel evidence that WARS2 facilitates PRV infection through its management of protein and lipid levels, presenting new avenues for developing preventative and therapeutic measures against PRV infections.

Characterization of humoral immune responses against SARS-CoV-2 accessory proteins in infected patients and mouse model

Yuming Li, Yanhong Tang, Xiaoqian Wang, Airu Zhu, Dongdong Liu, Yiyun He, Hu Guo, Jie Zheng, Xinzhuo Liu, Fengyu Chi, Yanqun Wang, Zhen Zhuang, Zhaoyong Zhang, Donglan Liu, Zhao Chen, Fang Li, Wei Ran, Kuai Yu, Dong Wang, Liyan Wen, Jianfen Zhuo, Yanjun Zhang, Yin Xi, Jingxian Zhao, Jincun Zhao, Jing Sun

2024, 39(3): 414 doi: 10.1016/j.virs.2024.04.005

Received: 05 November 2023 Accepted: 19 April 2024
Abstract [PDF 2495 KB] ScienceDirectESM
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, encodes several accessory proteins that have been shown to play crucial roles in regulating the innate immune response. However, their expressions in infected cells and immunogenicity in infected humans and mice are still not fully understood. This study utilized various techniques such as luciferase immunoprecipitation system (LIPS), immunofluorescence assay (IFA), and western blot (WB) to detect accessory protein-specific antibodies in sera of COVID-19 patients. Specific antibodies to proteins 3a, 3b, 7b, 8 and 9c can be detected by LIPS, but only protein 3a antibody was detected by IFA or WB. Antibodies against proteins 3a and 7b were only detected in ICU patients, which may serve as a marker for predicting disease progression. Further, we investigated the expression of accessory proteins in SARS-CoV-2-infected cells and identified the expressions of proteins 3a, 6, 7a, 8, and 9b. We also analyzed their ability to induce antibodies in immunized mice and found that only proteins 3a, 6, 7a, 8, 9b and 9c were able to induce measurable antibody productions, but these antibodies lacked neutralizing activities and did not protect mice from SARS-CoV-2 infection. Our findings validate the expression of SARS-CoV-2 accessory proteins and elucidate their humoral immune response, providing a basis for protein detection assays and their role in pathogenesis.

Integration of HiBiT into enteroviruses: A universal tool for advancing enterovirus virology research

Rui Yu, Xiaohong Li, Peng Zhang, Minghao Xu, Jitong Zhao, Jingjing Yan, Chenli Qiu, Jiayi Shu, Shuo Zhang, Miaomiao Kang, Xiaoyan Zhang, Jianqing Xu, Shuye Zhang

2024, 39(3): 422 doi: 10.1016/j.virs.2024.03.004

Received: 22 November 2023 Accepted: 11 March 2024
Abstract [PDF 2883 KB] ScienceDirectESM
The utilization of enteroviruses engineered with reporter genes serves as a valuable tool for advancing our understanding of enterovirus biology and its applications, enabling the development of effective therapeutic and preventive strategies. In this study, our initial attempts to introduce a NanoLuc luciferase (NLuc) reporter gene into recombinant enteroviruses were unsuccessful in rescuing viable progenies. We hypothesized that the size of the inserted tag might be a determining factor in the rescue of the virus. Therefore, we inserted the 11-amino-acid HiBiT tag into the genomes of enterovirus A71 (EV-A71), coxsackievirus A10 (CVA10), coxsackievirus A7 (CVA7), coxsackievirus A16 (CVA16), namely EV-A71-HiBiT, CVA16-HiBiT, CVA10-HiBiT, CVA7-HiBiT, and observed that the HiBiT-tagged viruses exhibited remarkably high rescue efficiency. Notably, the HiBiT-tagged enteroviruses displayed comparable characteristics to the wild-type viruses. A direct comparison between CVA16-NLuc and CVA16-HiBiT recombinant viruses revealed that the tiny HiBiT insertion had minimal impact on virus infectivity and replication kinetics. Moreover, these HiBiT-tagged enteroviruses demonstrated high genetic stability in different cell lines over multiple passages. In addition, the HiBiT-tagged viruses were successfully tested in antiviral drug assays, and the sensitivity of the viruses to drugs was not affected by the HiBiT tag. Ultimately, our findings provide definitive evidence that the integration of HiBiT into enteroviruses presents a universal, convenient, and invaluable method for advancing research in the realm of enterovirus virology. Furthermore, HiBiT-tagged enteroviruses exhibit great potential for diverse applications, including the development of antivirals and the elucidation of viral infection mechanisms.

Establishment and application of a surrogate model for human Ebola virus disease in BSL-2 laboratory

Wanying Yang, Wujian Li, Wujie Zhou, Shen Wang, Weiqi Wang, Zhenshan Wang, Na Feng, Tiecheng Wang, Ying Xie, Yongkun Zhao, Feihu Yan, Xianzhu Xia

2024, 39(3): 434 doi: 10.1016/j.virs.2024.03.010

Received: 17 November 2023 Accepted: 22 March 2024
Abstract [PDF 6985 KB] ScienceDirect
The Ebola virus (EBOV) is a member of the Orthoebolavirus genus, Filoviridae family, which causes severe hemorrhagic diseases in humans and non-human primates (NHPs), with a case fatality rate of up to 90%. The development of countermeasures against EBOV has been hindered by the lack of ideal animal models, as EBOV requires handling in biosafety level (BSL)-4 facilities. Therefore, accessible and convenient animal models are urgently needed to promote prophylactic and therapeutic approaches against EBOV. In this study, a recombinant vesicular stomatitis virus expressing Ebola virus glycoprotein (VSV-EBOV/GP) was constructed and applied as a surrogate virus, establishing a lethal infection in hamsters. Following infection with VSV-EBOV/GP, 3-week-old female Syrian hamsters exhibited disease signs such as weight loss, multi-organ failure, severe uveitis, high viral loads, and developed severe systemic diseases similar to those observed in human EBOV patients. All animals succumbed at 2-3 days post-infection (dpi). Histopathological changes indicated that VSV-EBOV/GP targeted liver cells, suggesting that the tissue tropism of VSV-EBOV/GP was comparable to wild-type EBOV (WT EBOV). Notably, the pathogenicity of the VSV-EBOV/GP was found to be species-specific, age-related, gender-associated, and challenge route-dependent. Subsequently, equine anti-EBOV immunoglobulins and a subunit vaccine were validated using this model. Overall, this surrogate model represents a safe, effective, and economical tool for rapid preclinical evaluation of medical countermeasures against EBOV under BSL-2 conditions, which would accelerate technological advances and breakthroughs in confronting Ebola virus disease.

An optimized high-throughput SARS-CoV-2 dual reporter trans-complementation system for antiviral screening in vitro and in vivo

Yingjian Li, Xue Tan, Jikai Deng, Xuemei Liu, Qianyun Liu, Zhen Zhang, Xiaoya Huang, Chao Shen, Ke Xu, Li Zhou, Yu Chen

2024, 39(3): 447 doi: 10.1016/j.virs.2024.03.009

Received: 04 December 2023 Accepted: 21 March 2024
Abstract [PDF 5827 KB] ScienceDirectESM
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still epidemic around the world. The manipulation of SARS-CoV-2 is restricted to biosafety level 3 laboratories (BSL-3). In this study, we developed a SARS-CoV-2 ΔN-GFP-HiBiT replicon delivery particles (RDPs) encoding a dual reporter gene, GFP-HiBiT, capable of producing both GFP signal and luciferase activities. Through optimal selection of the reporter gene, GFP-HiBiT demonstrated superior stability and convenience for antiviral evaluation. Additionally, we established a RDP infection mouse model by delivering the N gene into K18-hACE2 KI mouse through lentivirus. This mouse model supports RDP replication and can be utilized for in vivo antiviral evaluations. In summary, the RDP system serves as a valuable tool for efficient antiviral screening and studying the gene function of SARS-CoV-2. Importantly, this system can be manipulated in BSL-2 laboratories, decreasing the threshold of experimental requirements.

Development of a Měnglà virus minigenome and comparison of its polymerase complexes with those of other filoviruses

Shi-Zhe Xie, Ke Yao, Bei Li, Cheng Peng, Xing-Lou Yang, Zheng-Li Shi

2024, 39(3): 459 doi: 10.1016/j.virs.2024.03.011

Received: 06 December 2023 Accepted: 25 March 2024
Abstract [PDF 2845 KB] ScienceDirect
Ebola virus (EBOV) and Marburg virus (MARV), members of the Filoviridae family, are highly pathogenic and can cause hemorrhagic fevers, significantly impacting human society. Bats are considered reservoirs of these viruses because related filoviruses have been discovered in bats. However, due to the requirement for maximum containment laboratories when studying infectious viruses, the characterization of bat filoviruses often relies on pseudoviruses and minigenome systems. In this study, we used RACE technology to sequence the 3′-leader and 5′-trailer of Měnglà virus (MLAV) and constructed a minigenome. Similar to MARV, the transcription activities of the MLAV minigenome are independent of VP30. We further assessed the effects of polymorphisms at the 5′ end on MLAV minigenome activity and identified certain mutations that decrease minigenome reporter efficiency, probably due to alterations in the RNA secondary structure. The reporter activity upon recombination of the 3′-leaders and 5′-trailers of MLAV, MARV, and EBOV with those of the homologous or heterologous minigenomes was compared and it was found that the polymerase complex and leader and trailer sequences exhibit intrinsic specificities. Additionally, we investigated whether the polymerase complex proteins from EBOV and MARV support MLAV minigenome RNA synthesis and found that the homologous system is more efficient than the heterologous system. Remdesivir efficiently inhibited MLAV as well as EBOV replication. In summary, this study provides new information on bat filoviruses and the minigenome will be a useful tool for high-throughput antiviral drug screening.

Function investigation of p11.5 in ASFV infection

Dan Yin, Bin Shi, Renhao Geng, Yingnan Liu, Lang Gong, Hongxia Shao, Kun Qian, Hongjun Chen, Aijian Qin

2024, 39(3): 469 doi: 10.1016/j.virs.2024.05.007

Received: 29 November 2023 Accepted: 17 May 2024
Abstract [PDF 2103 KB] ScienceDirectESM
Virus replication relies on complex interactions between viral proteins. In the case of African swine fever virus (ASFV), only a few such interactions have been identified so far. In this study, we demonstrate that ASFV protein p72 interacts with p11.5 using co-immunoprecipitation and liquid chromatography-mass spectrometry (LC-MS). It was found that protein p72 interacts specifically with p11.5 at sites amino acids (aa) 1-216 of p72 and aa 1-68 of p11.5. To assess the importance of p11.5 in ASFV infection, we developed a recombinant virus (ASFVGZΔA137R) by deleting the A137R gene from the ASFVGZ genome. Compared with ASFVGZ, the infectious progeny virus titers of ASFVGZΔA137R were reduced by approximately 1.0 logs. In addition, we demonstrated that the growth defect was partially attributable to a higher genome copies-to-infectious virus titer ratios produced in ASFVGZΔA137R-infected MA104 cells than in those infected with ASFVGZ. This finding suggests that MA104 cells infected with ASFVGZΔA137R may generate larger quantities of noninfectious particles. Importantly, we found that p11.5 did not affect virus-cell binding or endocytosis. Collectively, we show for the first time the interaction between ASFV p72 and p11.5. Our results effectively provide the relevant information of the p11.5 protein. These results extend our understanding of complex interactions between viral proteins, paving the way for further studies of the potential mechanisms and pathogenesis of ASFV infection.

Nanobodies against African swine fever virus p72 and CD2v proteins as reagents for developing two cELISAs to detect viral antibodies

Jiahong Zhu, Qingyuan Liu, Liuya Li, Runyu Zhang, Yueting Chang, Jiakai Zhao, Siyu Liu, Xinyu Zhao, Xu Chen, Yani Sun, Qin Zhao

2024, 39(3): 478 doi: 10.1016/j.virs.2024.04.002

Received: 11 September 2023 Accepted: 01 April 2024
Abstract [PDF 3654 KB] ScienceDirectESM
African swine fever virus (ASFV) poses a significant threat to the global swine industry. Currently, there are no effective vaccines or treatments available to combat ASFV infection in pigs. The primary means of controlling the spread of the disease is through rapid detection and subsequent elimination of infected pig. Recently, a lower virulent ASFV isolate with a deleted EP402R gene (CD2v-deleted) has been reported in China, which further complicates the control of ASFV infection in pig farms. Furthermore, an EP402R-deleted ASFV variant has been developed as a potential live attenuated vaccine candidate strain. Therefore, it is crucial to develop detection methods that can distinguish wild-type and EP402R-deleted ASFV infections. In this study, two recombinant ASFV-p72 and -CD2v proteins were expressed using a prokaryotic system and used to immunize Bactrian camels. Subsequently, eight nanobodies against ASFV-p72 and ten nanobodies against ASFV-CD2v were screened. Following the production of these nanobodies with horse radish peroxidase (HRP) fusion proteins, the ASFV-p72-Nb2-HRP and ASFV-CD2v-Nb22-HRP fusions were selected for the development of two competitive ELISAs (cELISAs) to detect anti-ASFV antibodies. The two cELISAs exhibited high sensitivity, good specificity, repeatability, and stability. The coincidence rate between the two cELISAs and commercial ELISA kits was 98.6% and 97.6%, respectively. Collectively, the two cELISA for detecting antibodies against ASFV demonstrated ease of operation, a low cost, and a simple production process. The two cELISAs could determine whether pigs were infected with wild-type or CD2v-deleted ASFV, and could play an important role in monitoring ASFV infections in pig farms.

DNA vaccine prime and replicating vaccinia vaccine boost induce robust humoral and cellular immune responses against MERS-CoV in mice

Xiuli Shen, Shuhui Wang, Yanling Hao, Yuyu Fu, Li Ren, Dan Li, Wenqi Tang, Jing Li, Ran Chen, Meiling Zhu, Shuo Wang, Ying Liu, Yiming Shao

2024, 39(3): 490 doi: 10.1016/j.virs.2024.05.005

Received: 04 November 2023 Accepted: 15 May 2024
Abstract [PDF 1120 KB] ScienceDirectESM
As of December 2022, 2603 laboratory-identified Middle East respiratory syndrome coronavirus (MERS-CoV) infections and 935 associated deaths, with a mortality rate of 36%, had been reported to the World Health Organization (WHO). However, there are still no vaccines for MERS-CoV, which makes the prevention and control of MERS-CoV difficult. In this study, we generated two DNA vaccine candidates by integrating MERS-CoV Spike (S) gene into a replicating Vaccinia Tian Tan (VTT) vector. Compared to homologous immunization with either vaccine, mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune responses. The immunized mice produced robust binding antibodies and broad neutralizing antibodies against the EMC2012, England1 and KNIH strains of MERS-CoV. Prime-Boost immunization also induced strong MERS-S specific T cells responses, with high memory and poly-functional (CD107a-IFN-γ-TNF-α) effector CD8+ T cells. In conclusion, the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against MERS-CoV-S. This study not only provides a promising set of MERS-CoV vaccine candidates, but also proposes a heterologous sequential immunization strategy worthy of further development.

Calmodulin-like 5 promotes PEDV replication by regulating late-endosome synthesis and innate immune response

Wen-Jun Tian, Xiu-Zhong Zhang, Jing Wang, Jian-Feng Liu, Fu-Huang Li, Xiao-Jia Wang

2024, 39(3): 501 doi: 10.1016/j.virs.2024.05.006

Received: 06 December 2023 Accepted: 15 May 2024
Abstract [PDF 3964 KB] ScienceDirectESM
The infection caused by porcine epidemic diarrhea virus (PEDV) is associated with high mortality in piglets worldwide. Host factors involved in the efficient replication of PEDV, however, remain largely unknown. Our recent proteomic study in the virus-host interaction network revealed a significant increase in the accumulation of CALML5 (EF-hand protein calmodulin-like 5) following PEDV infection. A further study unveiled a biphasic increase of CALML5 in 2 and 12 h after viral infection. Similar trends were observed in the intestines of piglets in the early and late stages of the PEDV challenge. Moreover, CALML5 depletion reduced PEDV mRNA and protein levels, leading to a one-order-of-magnitude decrease in virus titer. At the early stage of PEDV infection, CALML5 affected the endosomal trafficking pathway by regulating the expression of endosomal sorting complex related cellular proteins. CALML5 depletion also suppressed IFN-β and IL-6 production in the PEDV-infected cells, thereby indicating its involvement in negatively regulating the innate immune response. Our study reveals the biological function of CALML5 in the virology field and offers new insights into the PEDV-host cell interaction.
Letters

Severe fever with thrombocytopenia syndrome virus infection attributed to cat contact: A case report in Beijing, China

Shuo Zhang, Yu Leng, Fa-Xue Zhang, Bo-Kang Fu, Bing-Zheng Wu, Jia-Hao Chen, Ning Cui, Ning Zhao, Wei Liu, Hao Li

2024, 39(3): 513 doi: 10.1016/j.virs.2024.03.006

Received: 24 December 2023 Accepted: 14 March 2024
Abstract [PDF 794 KB] ScienceDirectESM
Highlights1. SFTSV is detected in host-seeking ticks in rural-urban fringe areas in Beijing.2. SFTSV RNA, IgM, and neutralizing antibodies are detected in stray cats in Beijing.3. Multiple SFTSV genotypes naturally circulate within ticks in Beijing's urban zones.

A lethal mice model of recombinant vesicular stomatitis viruses for EBOV-targeting prophylactic vaccines evaluation

Hong-Qing Zhang, Zhe-Rui Zhang, Cheng-Lin Deng, Zhi-Ming Yuan, Bo Zhang

2024, 39(3): 516 doi: 10.1016/j.virs.2024.03.008

Received: 09 October 2023 Accepted: 18 March 2024
Abstract [PDF 1405 KB] ScienceDirectESM
Highlights1. The recombinant VSV-EBOV is highly lethal to IFNα/β/γ R-/- mice.2. The infected mice exhibit hyperviremia and distinct splenohepatic lesions.3. Virus replicon particle vaccine can protect all IFNα/β/γ R-/- mice against VSV-EBOV lethal challenge.4. This surrogate model can be used for EBOV vaccine evaluation.

Genetic characteristics of H1N1 influenza virus outbreak in China in early 2023

Xuanxuan Li, Zefeng Dong, Jiaming Li, Chuanran Dou, Deyu Tian, Zhenghai Ma, Wenjun Liu, George F. Gao, Yuhai Bi

2024, 39(3): 520 doi: 10.1016/j.virs.2024.05.003

Received: 25 October 2023 Accepted: 09 May 2024
Abstract [PDF 1801 KB] ScienceDirectESM
Highlights
1. H1N1 strains were collected from Hunan and Jiangsu provinces in early 2023 following the optimized COVID-19 strategy.
2. Phylogenic analysis revealed that the epidemic H1N1 viruses fell into different HA clades compared to vaccine strains.
3. Mutations on HA antigenic sites suggest antigenic drift in the epidemic H1N1 viruses versus vaccine strains.
4. A potential mismatch was found between recommended vaccine strains and the epidemic H1N1 viruses.
5. The expeditious, precise, and personalized vaccine update program for influenza virus may need to be put on the agenda.