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Virologica Sinica 2019年第6期34卷 610-617页

作者： Qiao Xue Huisheng Liu Qiaoying Zeng haixue zheng Qinghong Xue Xuepeng Cai Laboratory of Veterinary Microbiology College of Veterinary MedicineGansu Agricultural UniversityLanzhou 730070China State Key Laboratory of Veterinary Etiological Biology National Foot and Mouth Diseases Reference LaboratoryKey Laboratory of Animal Virology of Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730046China China Institute of Veterinary Drug Control Beijing 100081China

Foot-and-mouth disease virus(FMDV)can infect domestic and wild cloven-hoofed *** non-structural protein 3D plays an important role in FMDV replication and ***,the interaction partners of 3D,and the effects of those interactions on FMDV replication,remain incompletely *** the present study,using the yeast two-hybrid system,we identified a porcine cell protein,DEAD-box RNA helicase 1(DDX1),which interacted with FMDV *** DDX1-3D interaction was further confirmed by co-immunoprecipitation experiments and an indirect immunofluorescence assay(IFA)in porcine kidney 15(PK-15)***1 was reported to either inhibit or facilitate viral replication and regulate host innate immune ***,the roles of DDX1 during FMDV infection remain *** results revealed that DDX1 inhibited FMDV replication in an ATPase/helicase activity-dependent *** addition,DDX1 stimulated IFN-p activation in FMDV-infected ***,our results expand the body of knowledge regarding the role of DDX1 in FMDV infection.

关键词： Foot-and-mouth disease virus(FMDV) Interaction DEAD-box RNA helicase 1(DDX1) Antiviral function Interferon

Foot-and-Mouth Disease Virus Inhibits RIP2 Protein Expression to Promote Viral Replication

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Virologica Sinica 2021年第4期36卷 608-622页

作者： Huisheng Liu Qiao Xue Zixiang Zhu Fan Yang Weijun Cao Xiangtao Liu haixue zheng State Key Laboratory of Veterinary Etiological Biology National Foot and Mouth Diseases Reference LaboratoryKey Laboratory of Animal Virology of Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730046China

Receptors interaction protein 2(RIP2)is a specific adaptor molecule in the downstream of *** role of RIP2 during foot-and-mouth disease virus(FMDV)infection remains ***,our results showed that RIP2 inhibited FMDV replication and played an important role in the activation of IFN-βand NF-κB signal pathways during FMDV *** infection triggered RIP2 transcription,while it reduced the expression of RIP2 *** analysis showed that FMDV 2B,2C,3C^(pro),and L^(pro) proteins were responsible for inducing the reduction of RIP2 protein.3C^(pro) and L^(pro) are viral proteinases that can induce the cleavage or reduction of many host proteins and block host protein *** carboxyl terminal 105-C114 and 135-C144 regions of 2B were essential for reduction of *** results also showed that the N terminal 1-61 region of 2C were essential for the reduction of *** 2C-induced reduction of RIP2 was dependent on inducing the reduction of poly(A)-binding protein 1(PABPC1).The interaction between RIP2 and 2C was observed in the context of viral infection,and the residues 1-61 were required for the *** data clarify novel mechanisms of reduction of RIP2 mediated by FMDV.

关键词： Foot-and-mouth disease virus(FMDV) Receptors interaction protein 2(RIP2) PABPC1 2C Immune evasion

The Distribution of Different Clades of Seneca Valley Viruses in Guangdong Province,China

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Virologica Sinica 2018年第5期33卷 394-401页

作者： Pan Chen Fan Yang Weijun Cao Huanan Liu Keshan Zhang Xiangtao Liu Zhiwen Xu Zixiang Zhu haixue zheng State Key Laboratory of Veterinary Etiological Biology National Foot and Mouth Diseases Reference LaboratoryKey Laboratory of Animal Virology of Ministry of Agriculture Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences Animal Biotechnology Center Key Laboratory of Animal Disease and Human Health of Sichuan Province Sichuan Agricultural University

Seneca Valley virus (SVV), a newly determined etiological agent of vesicular disease in swine, causes porcine idiopathic disease and occasional acute death in piglets. Recently, an increased number of SVV infection cases have been reported in the United States (US) and China, resulting in significant economic losses to the swine industry. The first identification of SVV in China was reported in Guangdong Province, a major swine producing province. The cases of SVV were continuously reported in Guangdong in 2015 and 2016. However, the spread of SVV in Guangdong in 2017 remains *** this study, we determined two new SVV strains, CH-GD-2017-1 and CH-GD-2017-2, from Guangdong. The genetic analysis suggested that the two Guangdong strains showed different characteristics to previous Guangdong strains. They showed lower nucleotide similarity with strains isolated in 2015 and 2016, and were more similar to the US *** analyses indicated that the new strains were clustered in a different clade with previous Guangdong *** found 28 mutated amino acids in the new strains, compared with the first Guangdong strain, SVV CH-01-2015. In the geographic analysis, we found that the US and China reported more SVV cases than other countries, and most of the SVV cases were reported in east and central China—of which, Guangdong Province is one of the major epidemic regions. In conclusion, our findings indicate that SVV continued to spread in Guangdong Province in 2017, and two different clades of SVVs have emerged in this region.

关键词： Seneca Valley virus (SVV) Genomic sequence Phylogenetic tree Epidemiological analysis

Identification of African swine fever virus MGF505-2R as a potent inhibitor of innate immunity in vitro

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Virologica Sinica 2023年第1期38卷 84-95页

作者： Huaguo Huang Wen Dang zhengwang Shi Mingyang Ding Fan Xu Tao Li Tao Feng haixue zheng Shuqi Xiao College of Veterinary Medicine Northwest A&F UniversityYangling712100China State Key Laboratory of Veterinary Etiological Biology College of Veterinary MedicineLanzhou UniversityLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou730046China College of Veterinary Medicine Gansu Agricultural UniversityLanzhou730070China

African swine fever(ASF)is etiologically an acute,highly contagious and hemorrhagic disease caused by African swine fever virus(ASFV).Due to its genetic variation and phenotypic diversity,until now,no efficient commercial vaccines or therapeutic options are *** ASFV genome contains a conserved middle region and two flexible ends that code for five multigene families(MGFs),while the biological functions of the MGFs are not fully ***,ASFV MGF505-2R-deficient mutant ASFV-Δ2R was constructed based on a highly virulent genotype II field isolate ASFV CN/GS/2018 currently circulating in *** profiling demonstrated that ASFV-Δ2R was capable of inducing a larger number of differentially expressed genes(DEGs)compared with ASFV CN/GS/*** clustering of up-regulated DEGs revealed that ASFV-Δ2R induced the most dramatic expression of interferon-related genes and inflammatory and innate immune genes,as further validated by *** GO and KEGG pathway analysis identified significantly enriched pathways involved in pathogen recognition and innate antiviral ***,pharmacological activation of those antiviral immune responses by exogenous cytokines,including type I/II IFNs,TNF-αand IL-1β,exerted combinatory effects and synergized in antiviral capacity against ASFV ***,MGF505-2R is a newly identified inhibitor of innate immunity potentially implicated in immune evasion.

关键词： African swine fever virus(ASFV) Multigene families(MGFs) MGF505-2R Differentially expressed genes(DEGs)

African Swine Fever Virus MGF-110-9L-deficient Mutant Has Attenuated Virulence in Pigs

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Virologica Sinica 2021年第2期36卷 187-195页

作者： Dan Li Yinguang Liu Xiaolan Qi Yuan Wen Pan Li Zhao Ma Yongjie Liu haixue zheng Zhijie Liu State Key Laboratory of Veterinary Etiological Biology and OIE/National Foot and Mouth Disease Reference Laboratory Lanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730046China

African swine fever virus(ASFV)is the etiological agent of African swine fever(ASF),an often lethal disease in domestic and wild *** represents a major threat to the swine industry ***,no commercial vaccine is available because of the complexity of ASFV or biosecurity *** attenuated viruses that are naturally isolated or genetically manipulated have demonstrated reliable protection against homologous ASFV strain *** the present study,a mutant ASFV strain with the deletion of ASFV MGF-110-9L(ASFV-D9L)was generated from a highly virulent ASFV CN/GS/2018 parental strain,a genotypeⅡ*** to the parental ASFV isolate,deletion of the MGF-110-9L gene significantly decreased the ability of ASFV-D9L to replicate in vitro in primary swine macrophage cell *** majority of animals inoculated intramuscularly with a low dose of ASFV-D9L(10 HAD50)remained clinically normal during the 21-day observational *** of five ASFV-D9L-infected animals displayed low viremia titers and low virus shedding and developed a strong virus-specific antibody response,indicating partial attenuation of the ASFV-D9L strain in *** findings imply the potential usefulness of the ASFV-D9L strain for further development of ASF control measures.

关键词： African swine fever virus(ASFV) MGF-110-9L Mutant Attenuated virulence Pig

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FoxJ1 inhibits African swine fever virus replication and viral S273R protein decreases the expression of FoxJ1 to impair its antiviral effect

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Virologica Sinica 2022年第3期37卷 445-454页

作者： Caina Ma Shasha Li Fan Yang Weijun Cao Huisheng Liu Tao Feng Keshan Zhang Zixiang Zhu Xiangtao Liu Yonghao Hu haixue zheng College of Veterinary Medicine Gansu Agricultural UniversityLanzhou730070China State Key Laboratory of Veterinary Etiological Biology National Foot and Mouth Diseases Reference LaboratoryKey Laboratory of Animal Virology of Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou730046China

African swine fever(ASF)is a highly pathogenic swine infectious disease that affects domestic pigs and wild boar,which is caused by the African swine fever virus(ASFV).ASF has caused huge economic losses to the pig industry and seriously threatens global food security and livestock *** date,there is no safe and effective commercial vaccine against *** the underlying mechanisms of ASFV-host interplay is critical for developing effective vaccines and drugs against *** the present study,RNA-sequencing,RT-qPCR and Western blotting analysis revealed that the transcriptional and protein levels of the host factor FoxJ1 were significantly down-regulated in primary porcine alveolar macrophages(PAMs)infected by ***-qPCR analysis showed that overexpression of FoxJ1 upregulated the transcription of type I interferon and interferon stimulating genes(ISGs)induced by poly(dA:dT).FoxJ1 revealed a function to positively regulate innate immune response,therefore,suppressing the replication of *** addition,Western blotting analysis indicated that FoxJ1 degraded ASFV MGF505-2R and E165R proteins through autophagy ***,RT-qPCR and Western blotting analysis showed that ASFV S273R inhibited the expression of ***,we determined that FoxJ1 plays an antiviral role against ASFV replication,and ASFV protein impairs FoxJ1-mediated antiviral effect by degradation of *** findings provide new insights into the antiviral function of FoxJ1,which might help design antiviral drugs or vaccines against ASFV infection.

关键词： African swine fever virus(ASFV) FoxJ1 ISGs MGF505-2R E165R S273R

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Virologica Sinica 2023年第5期38卷 813-826页

作者： Yang Li Lele Xu Dian Jiao Zifang zheng Zhihao Chen Yang Jing Zhiwei Li Zhiqian Maa Yingtong Feng Xuyang Guo Yumiao Wang Yuan He haixue zheng Shuqi Xiao State Key Laboratory for Animal Disease Control and Prevention College of Veterinary MedicineLanzhou UniversityLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou730046China College of Veterinary Medicine Northwest A&F UniversityYangling712100China

Porcine reproductive and respiratory syndrome(PRRS)is one of the most significant diseases affecting the pig industry *** PRRSV mutation rate is the highest among the RNA *** date,NADC30-like PRRSV and highly pathogenic PRRSV(HP-PRRSV)are the dominant epidemic strains in China;however,commercial vaccines do not always provide sufficient cross-protection,and the reasons for insufficient protection are *** study isolated a wild-type NADC30-like PRRSV,SX-YL1806,from Shaanxi *** challenge experiments in piglets showed that commercial modified live virus(MLV)vaccines provided good protection against ***,it could not provide sufficient protection against the novel strain *** explore the reasons for this phenomenon,we compared the genomic homology between the MLV strain and HP-PRRSV or NADC30-like PRRSV and found that the MLV strain had a lower genome similarity with NADC30-like *** neutralization assay showed that MLV-immune serum slightly promoted the homologous HP-PRRSV replication and significantly promoted the heterologous NADC30-like PRRSV strain replication in vitro,suggesting that antibody-dependent enhancement(ADE)might also play a role in decreasing MLV protective *** findings expand our understanding of the potential factors affecting the protective effect of PRRSV MLV vaccines against the NADC30-like strains.

关键词： NADC30-like PRRSV Modified live virus(MLV)vaccines Genomic similarity Antibody dependent enhancement(ADE) Cross protection

KIF5B-mediated internalization of FMDV promotes virus infection

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Virologica Sinica 2024年第3期39卷 378-389页

作者： Wei Zhang Fan Yang Yang Yang Weijun Cao Wenhua Shao Jiali Wang Mengyao Huang Zhitong Chen Xiaoyi Zhao Weiwei Li Zixiang Zhu haixue zheng State Key Laboratory for Animal Disease Control and Prevention College of Veterinary MedicineLanzhou UniversityLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730000China Gansu Province Research Center for Basic Disciplines of Pathogen Biology Lanzhou 730046China

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 *** this study,we found that kinesin family member 5B(KIF5B)plays a vital role during FMDV ***,we confirmed the interaction between KIF5B and FMDV structural protein VP1 by co-immunoprecipitation(Co-IP)and co-localization in FMDV-infected *** particular,the stalk[amino acids(aa)413–678]domain of KIF5B was indispensable for KIF5B-VP1 ***,overexpression of KIF5B dramatically enhanced FMDV replication;consistently,knockdown or knockout of KIF5B suppressed FMDV ***,we also demonstrated that KIF5B promotes the internalization of FMDV via regulating clathrin ***5B also promotes the transmission of viral particles to early and late endosomes during the early stages of *** conclusion,our results demonstrate that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating and intracellular *** study may provide a new therapeutic target for developing FMDV antiviral drugs.

关键词： FMDV VP1 protein KIF5B Endosome Clathrin

Porcine Picornavirus 3C Protease Degrades PRDX6 to Impair PRDX6-mediated Antiviral Function

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Virologica Sinica 2021年第6期36卷 948-957页

作者： Congcong Wang Huanhuan Feng Xiangle Zhang Kangli Li Fan Yang Weijun Cao Huisheng Liu Lili Gao Zhaoning Xue Xiangtao Liu Zixiang Zhu haixue zheng State Key Laboratory of Veterinary Etiological Biology OIE/National Foot and Mouth Diseases Reference LaboratoryKey Laboratory of Animal Virology of Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730046China

Peroxiredoxin-6(PRDX6)is an antioxidant enzyme with both the activities of peroxidase and phospholipase A2(PLA2),which is involved in regulation of many cellular ***,the function of PRDX6 during virus infection remains *** this study,we found that the abundance of PRDX6 protein was dramatically decreased in foot-and-mouth disease virus(FMDV)infected *** of PRDX6 inhibited FMDV *** contrast,knockdown of PRDX6 expression promoted FMDV replication,suggesting an antiviral role of *** explore whether the activity of peroxidase and PLA2 was associated with PRDX6-mediated antiviral function,a specific inhibitor of PLA2(MJ33)and a specific inhibitor of peroxidase activity(mercaptosuccinate)were used to treat the cells before FMDV *** results showed that incubation of MJ33 but not mercaptosuccinate promoted FMDV ***,overexpression of PRDX6 slightly enhanced type I interferon *** further determined that the viral 3Cprowas responsible for degradation of PRDX6,and 3Cpro-induced reduction of PRDX6 was independent of the proteasome,lysosome,and caspase *** protease activity of 3Cprowas required for induction of PRDX6 ***,PRDX6 suppressed the replication of another porcine picornavirus Senecavirus A(SVA),and the 3Cproof SVA induced the reduction of PRDX6 through its proteolytic activity as ***,our results suggested that PRDX6 plays an important antiviral role during porcine picornavirus infection,and the viral 3Cproinduces the degradation of PRDX6 to overcome PRDX6-mediated antiviral function.

关键词： Porcine picornavirus Peroxiredoxin-6(PRDX6) 3Cpro Phospholipase A2(PLA2) Antagonism

Porcine epidemic diarrhea virus nsp14 inhibits NF-κB pathway activation by targeting the IKK complex and p65

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Animal Diseases 2021年第3期1卷 162-172页

作者： Shasha Li Fan Yang Caina Ma Weijun Cao Jinping Yang Zhenxiang Zhao Hong Tian Zixiang Zhu haixue zheng State Key Laboratory of Veterinary Etiological Biology National Foot and Mouth Diseases Reference LaboratoryKey Laboratory of Animal Virology of Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhouGansu 730046China

Coronaviruses(CoVs)are a group of related enveloped RNA viruses that have severe consequences in a wide variety of animals by causing respiratory,enteric or systemic *** epidemic diarrhea virus(PEDV)is an economically important CoV distributed worldwide that causes diarrhea in ***14 is a nonstructural protein of PEDV that is involved in regulation of innate immunity and viral ***,the function and mechanism by which nsp14 modulates and manipulates host immune responses remain largely ***,we report that PEDV nsp14 is an NF-κB pathway *** PEDV nsp14 protein remarkably decreases SeV-,poly(I:C)-and TNF-α-induced NF-κB ***,expression of proinflammatory cytokines is suppressed by ***14 inhibits the phosphorylation of IKKs by interacting with IKKs and ***,nsp14 suppresses TNF-α-induced phosphorylation and nuclear import of *** nsp14 considerably increases PEDV *** results suggest a novel mechanism employed by PEDV to suppress the host antiviral response,providing insights that can guide the development of antivirals against CoVs.

关键词： CoVs PEDV nsp14 NF-κB innate immunity