2018年第二期JVI国内学者文章汇总

rentianyixu · 发表于 2018-1-13 21:04:06

1.A 3.0-Angstrom Resolution Cryo-Electron Microscopy Structure and Antigenic Sites of Coxsackievirus A6-Like Particles

[size=0.85em]aNational Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
[size=0.85em]bShanghai Science Research Center, Chinese Academy of Sciences, Shanghai, China
[size=0.85em]cJoint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou, China
[size=0.85em]dJoint Center for Infection and Immunity, Institut Pasteur of Shanghai, Chinese Academy of Science, Shanghai, China
[size=0.85em]eVaccine Research Center, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
[size=0.85em]fMarkey Center for Structural Biology, Department of Biological Sciences, Purdue University, West Lafayette, Indiana, USA

ABSTRACT

Coxsackievirus A6 (CVA6) has recently emerged as one of the predominant causative agents of hand, foot, and mouth disease (HFMD). The structure of the CVA6 mature viral particle has not been solved thus far. Our previous work shows that recombinant virus-like particles (VLPs) of CVA6 represent a promising CVA6 vaccine candidate. Here, we report the first cryo-electron microscopy (cryo-EM) structure of the CVA6 VLP at 3.0-Å resolution. The CVA6 VLP exhibits the characteristic features of enteroviruses but presents an open channel at the 2-fold axis and an empty, collapsed VP1 pocket, which is broadly similar to the structures of the enterovirus 71 (EV71) VLP and coxsackievirus A16 (CVA16) 135S expanded particle, indicating that the CVA6 VLP is in an expanded conformation. Structural comparisons reveal that two common salt bridges within protomers are maintained in the CVA6 VLP and other viruses of the Enterovirus genus, implying that these salt bridges may play a critical role in enteroviral protomer assembly. However, there are apparent structural differences among the CVA6 VLP, EV71 VLP, and CVA16 135S particle in the surface-exposed loops and C termini of subunit proteins, which are often antigenic sites for enteroviruses. By immunological assays, we identified two CVA6-specific linear B-cell epitopes (designated P42 and P59) located at the GH loop and the C-terminal region of VP1, respectively, in agreement with the structure-based prediction of antigenic sites. Our findings elucidate the structural basis and important antigenic sites of the CVA6 VLP as a strong vaccine candidate and also provide insight into enteroviral protomer assembly.

Address correspondence to Zhong Huang, huangzhong@ips.ac.cn, or Yao Cong, cong@sibcb.ac.cn.
J.C. and C.Z. contributed equally to this article.
Citation Chen J, Zhang C, Zhou Y, Zhang X, Shen C, Ye X, Jiang W, Huang Z, Cong Y. 2018. A 3.0-angstrom resolution cryo-electron microscopy structure and antigenic sites of coxsackievirus A6-like particles. J Virol 92:e01257-17. https://doi.org/10.1128/JVI.01257-17.

rentianyixu · 发表于 2018-1-13 21:06:20

2.Identification of a Critical and Conformational Neutralizing Epitope in Human Adenovirus Type 4 Hexon

[size=0.85em]aState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
[size=0.85em]bKey Laboratory of Food Safety, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
[size=0.85em]cState Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macao, China
[size=0.85em]dInstitute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China

ABSTRACT

Human adenovirus type 4 (HAdV-4) is an epidemic virus that contributes to serious acute respiratory disease (ARD) in both pediatric and adult patients. However, no licensed drug or vaccine is currently available to the civilian population. The identification of neutralizing epitopes of HAdV-4 should allow the development of a novel antiviral vaccine and a novel gene transfer vector, and an effective neutralizing monoclonal antibody (MAb) will be useful in developing appropriate antiviral drugs. In this study, we report that MAb MN4b shows strong neutralizing activity against HAdV-4. MN4b recognizes a conformational epitope (418AGSEK422) within hypervariable region 7 (HVR7). Mutations within this site permitted HAdV-4 mutants to escape neutralization by MN4b and to resist neutralization by animal and human anti-HAdV-4 sera. A recombinant virus, rAd3-A4R7-1, containing the identified neutralizing epitope in the HVR7 region of HAdV-3 hexon, successfully induced antiserum that inhibited HAdV-4 infection. These results indicate that a small surface loop of HAdV-4 hexon is a critical neutralization epitope for this virus. The generation of MN4b and the identification of this neutralizing epitope may be useful in developing therapeutic treatment, a subunit vaccine, and a novel vector that can escape preexisting neutralization for HAdV-4.

Address correspondence to Rong Zhou, zhourong@gird.cn, or Hui Wang, huiwang@sibs.ac.cn.
X.T., H.Q., and Z.Z. contributed equally to this research.
Citation Tian X, Qiu H, Zhou Z, Wang S, Fan Y, Li X, Chu R, Li H, Zhou R, Wang H. 2018. Identification of a critical and conformational neutralizing epitope in human adenovirus type 4 hexon. J Virol 92:e01643-17. https://doi.org/10.1128/JVI.01643-17.

rentianyixu · 发表于 2018-1-13 21:07:34

3.VP1 and VP3 Are Required and Sufficient for Translation Initiation of Uncapped Infectious Bursal Disease Virus Genomic Double-Stranded RNA

[size=0.85em]aDepartment of Veterinary Medicine, College of Animal Science and Technology, Zhejiang A&F University, Hangzhou, Zhejiang Province, China
[size=0.85em]bDepartment of Biological Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, Jiangsu Province, China

ABSTRACT

Infectious bursal disease virus (IBDV) is a bisegmented double-strand RNA (dsRNA) virus of the Birnaviridae family. While IBDV genomic dsRNA lacks a 5′ cap, the means by which the uncapped IBDV genomic RNA is translated effectively is unknown. In this study, we describe a cap-independent pathway of translation initiation of IBDV uncapped RNA that relies on VP1 and VP3. We show that neither purified IBDV genomic dsRNA nor the uncapped viral plus-sense RNA transcripts were directly translated and rescued into infectious viruses in host cells. This defect in translation of the uncapped IBDV genomic dsRNA was rescued by trans-supplementation of the viral proteins VP1 and VP3 which was dependent on both the intact polymerase activity of VP1 and the dsRNA binding activity of VP3. Deletion analysis showed that both 5′ and 3′ untranslated regions (UTRs) of IBDV dsRNA were essential for VP1/VP3-dependent translation initiation. Significantly, VP1 and VP3 could also mediate the recovery of infectious IBDV from the authentic minus-sense strand of IBDV dsRNA. Moreover, downregulation or inhibition of the cap-binding protein eIF4E did not decrease but, rather, enhanced the VP1/VP3-mediated translation of the uncapped IBDV RNA. Collectively, our findings for the first time reveal that VP1 and VP3 compensate for the deficiency of the 5′ cap and replace eIF4E to confer upon the uncapped IBDV RNA the ability to be translated and rescued into infectious viruses.

Address correspondence to Hebin Liu, hb1liu@foxmail.com.
Citation Ye C, Wang Y, Zhang E, Han X, Yu Z, Liu H. 2018. VP1 and VP3 are required and sufficient for translation initiation of uncapped infectious bursal disease virus genomic double-stranded RNA. J Virol 92:e01345-17. https://doi.org/10.1128/JVI.01345-17.

rentianyixu · 发表于 2018-1-13 21:11:29

4.Emergence and Adaptation of a Novel Highly Pathogenic H7N9 Influenza Virus in Birds and Humans from a 2013 Human-Infecting Low-Pathogenic Ancestor

[size=0.85em]aNational and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
[size=0.85em]bCenter for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing, China
[size=0.85em]cCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
[size=0.85em]dInstitute of Pathogen Biology, Taishan Medical College, Taian, Shandong, China
[size=0.85em]eKey Laboratory of Zoonoses, Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Guangzhou, China
[size=0.85em]fCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
[size=0.85em]gGuangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
[size=0.85em]hKey Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou, China
[size=0.85em]iMarie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences, and Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
[size=0.85em]jCollege of Global Change and Earth System Science, Beijing Normal University, Beijing, China
[size=0.85em]kCentre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
[size=0.85em]lUniversity of Chinese Academy of Sciences, Beijing, China
[size=0.85em]mSavaid Medical School, University of Chinese Academy of Sciences, Beijing, China

ABSTRACT

Since its emergence in 2013, the H7N9 low-pathogenic avian influenza virus (LPAIV) has been circulating in domestic poultry in China, causing five waves of human infections. A novel H7N9 highly pathogenic avian influenza virus (HPAIV) variant possessing multiple basic amino acids at the cleavage site of the hemagglutinin (HA) protein was first reported in two cases of human infection in January 2017. More seriously, those novel H7N9 HPAIV variants have been transmitted and caused outbreaks on poultry farms in eight provinces in China. Herein, we demonstrate the presence of three different amino acid motifs at the cleavage sites of these HPAIV variants which were isolated from chickens and humans and likely evolved from the preexisting LPAIVs. Animal experiments showed that these novel H7N9 HPAIV variants are both highly pathogenic in chickens and lethal to mice. Notably, human-origin viruses were more pathogenic in mice than avian viruses, and the mutations in the PB2 gene associated with adaptation to mammals (E627K, A588V, and D701N) were identified by next-generation sequencing (NGS) and Sanger sequencing of the isolates from infected mice. No polymorphisms in the key amino acid substitutions of PB2 and HA in isolates from infected chicken lungs were detected by NGS. In sum, these results highlight the high degree of pathogenicity and the valid transmissibility of this new H7N9 variant in chickens and the quick adaptation of this new H7N9 variant to mammals, so the risk should be evaluated and more attention should be paid to this variant.

Address correspondence to George F. Gao, gaof@im.ac.cn, or Ming Liao, mliao@scau.edu.cn.
W.Q., W.J., and D.L. contributed equally to this article.
Citation Qi W, Jia W, Liu D, Li J, Bi Y, Xie S, Li B, Hu T, Du Y, Xing L, Zhang J, Zhang F, Wei X, Eden J-S, Li H, Tian H, Li W, Su G, Lao G, Xu C, Xu B, Liu W, Zhang G, Ren T, Holmes EC, Cui J, Shi W, Gao GF, Liao M. 2018. Emergence and adaptation of a novel highly pathogenic H7N9 influenza virus in birds and humans from a 2013 human-infecting low-pathogenic ancestor. J Virol 92:e00921-17. https://doi.org/10.1128/JVI.00921-17.

rentianyixu · 发表于 2018-1-13 21:14:08

5.Inducible MicroRNA-3570 Feedback Inhibits the RIG-I-Dependent Innate Immune Response to Rhabdovirus in Teleost Fish by Targeting MAVS/IPS-1

[size=0.85em]aCollege of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China
[size=0.85em]bLaboratory of Fish Biogenetics & Immune Evolution, College of Marine Science, Zhejiang Ocean University, Zhoushan, China

ABSTRACT

Effectively recognizing invading viruses and subsequently inducing innate antiviral immunity are essential for host antiviral defense. Although these processes are closely regulated by the host to maintain immune balance, viruses have evolved the ability to downregulate or upregulate these processes for their survival. MicroRNAs (miRNAs) are a family of small noncoding RNAs that play vital roles in modulating host immune response. Accumulating evidence demonstrates that host miRNAs as mediators are involved in regulating viral replication and host antiviral immunity in mammals. However, the underlying regulatory mechanisms in fish species are still poorly understood. Here, we found that rhabdovirus infection significantly upregulated host miR-3570 expression in miiuy croaker macrophages. Induced miR-3570 negatively modulated RNA virus-triggered type I interferon (IFN) and antiviral gene production, thus facilitating viral replication. Furthermore, miR-3570 was found to target and posttranscriptionally downregulate mitochondrial antiviral signaling protein (MAVS), which functions as a platform for innate antiviral signal transduction. Moreover, we demonstrated that miR-3570 suppressed the expression of MAVS, thereby inhibiting MAVS-mediated NF-κB and IRF3 signaling. The collective results demonstrated a novel regulation mechanism of MAVS-mediated immunity during RNA viral infection by miRNA.

Address correspondence to Tianjun Xu, tianjunxu@163.com.
Citation Xu T, Chu Q, Cui J, Bi D. 2018. Inducible microRNA-3570 feedback inhibits the RIG-I-dependent innate immune response to rhabdovirus in teleost fish by targeting MAVS/IPS-1. J Virol 92:e01594-17. https://doi.org/10.1128/JVI.01594-17.

cao1976 · 发表于 2018-1-14 06:48:42

学习了，多谢楼主分享

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