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Ancient dormant virus remnant ERVW-1 drives ferroptosis via degradation of GPX4 and SLC3A2 in schizophrenia

Virologica Sinica 2024年第1期39卷 31-43页

作者： Dongyan Zhang Xiulin Wu Xing Xue Wenshi Li Ping Zhou Zhao Lv Kexin Zhao Fan Zhu State Key laboratory of virology and Department of Medical Microbiology School of Basic Medical SciencesWuhan UniversityWuhan430071China Hubei Province Key laboratory of Allergy&immunology Wuhan UniversityWuhan430071China

Human endogenous retroviruses(HERVs)are remnants of retroviral infections in human germline cells from millions of years *** these,ERVW-1(also known as HERV-W-ENV,ERVWE1,or ENVW)encodes the envelope protein of the HERV-W family,which contributes to the pathophysiology of ***,neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with ***,our bioinformatics analysis showed that differentially expressed genes in the human prefrontal cortex RNA microarray dataset(GSE53987)were mainly related to ferroptosis and its associated *** data demonstrated significantly lower expression levels of ferroptosis-related genes,particularly Glutathione peroxidase 4(GPX4)and solute carrier family 3 member 2(SLC3A2),in schizophrenia patients compared to normal *** in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in *** indicated that ERVW-1 increased iron levels,malondialdehyde(MDA),and transferrin receptor protein 1(TFR1)expression while decreasing glutathione(GSH)levels and triggering the loss of mitochondrial membrane potential,suggesting that ERVW-1 can induce *** research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter ***,Ferrostatin-1(Fer-1),the ferroptosis inhibitor,reversed the iron accumulation and mitochondrial membrane potential loss,as well as restored the expressions of ferroptosis markers GSH,MDA,and TFR1 induced by *** conclusion,ERVW-1 could promote ferroptosis by downregulating the expression of GPX4 and SLC3A2,revealing a novel mechanism by which ERVW-1 contributes to neuronal cell death in schizophrenia.

关键词： ERVW-1 Glutathione peroxidase 4(GPX4) Solute carrier family 3 member 2(SLC3A2) Ferroptosis Schizophrenia

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Cross-species transmission and host range genes in poxviruses

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Virologica Sinica 2024年第2期39卷 177-193页

作者： Chen-Hui Yang A-Ling Song Ye Qiu Xing-Yi Ge College of Biology Hunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha410012China

The persistent epidemic of human mpox, caused by mpox virus (MPXV), raises concerns about the future spread ofMPXV and other poxviruses. MPXV is a typical zoonotic virus which can infect human and cause smallpox-likesymptoms. MPXV belongs to the Poxviridae family, which has a relatively broad host range from arthropods tovertebrates. Cross-species transmission of poxviruses among different hosts has been frequently reported andresulted in numerous epidemics. Poxviruses have a complex linear double-strand DNA genome that encodeshundreds of proteins. Genes related to the host range of poxvirus are called host range genes (HRGs). This reviewbriefly introduces the taxonomy, phylogeny and hosts of poxviruses, and then comprehensively summarizes thecurrent knowledge about the cross-species transmission of poxviruses. In particular, the HRGs of poxvirus aredescribed and their impacts on viral host range are discussed in depth. We hope that this review will provide acomprehensive perspective about the current progress of researches on cross-species transmission and HRGvariation of poxviruses, serving as a valuable reference for academic studies and disease control in the future.

关键词： Poxvirus Host range gene(HRG) Host spectrum Cross-species transmission

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PABP-driven secondary condensed phase within RSV inclusion bodies activates viral mRNAs for ribosomal recruitment

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Virologica Sinica 2024年第2期39卷 235-250页

作者： Qiang Zhang Hanzhe Ye Cong Liu Haiwu Zhou Mingbin He Xiaodong Liang Yu Zhou Kun Wang Yali Qin Zhifei Li Mingzhou Chen State Key laboratory of virology and Modern virology Research Center College of Life SciencesWuhan UniversityWuhan430072China Taikang Center for Life and Medical Sciences Wuhan UniversityWuhan430072China Hubei Jiangxia laboratory Wuhan430200China

Inclusion bodies(IBs)of respiratory syncytial virus(RSV)are formed by liquid-liquid phase separation(LLPS)and contain internal structures termed“IB-associated granules”(IBAGs),where anti-termination factor M2-1 and viral mRNAs are ***,the mechanism of IBAG formation and the physiological function of IBAGs are ***,we found that the internal structures of RSV IBs are actual M2-1-free viral messenger ribonucleoprotein(mRNP)condensates formed by secondary ***,the RSV nucleoprotein(N)and M2-1 interact with and recruit PABP to IBs,promoting PABP to bind viral mRNAs transcribed in IBs by RNArecognition motif and drive secondary phase ***,PABP-eIF4G1 interaction regulates viral mRNP condensate composition,thereby recruiting specific translation initiation factors(eIF4G1,eIF4E,eIF4A,eIF4B and eIF4H)into the secondary condensed phase to activate viral mRNAs for ribosomal *** study proposes a novel LLPS-regulated translation mechanism during viral infection and a novel antiviral strategy via targeting on secondary condensed phase.

关键词： Respiratory syncytial virus(RSV) Inclusion bodies(IBs) Biomolecular condensates Liquid-liquid phase separation(LLPS) Secondary condensed phase mRNA activation

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Endogenous retrovirus activation: potential for immunology and clinical applications

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National Science Review 2024年第4期11卷 21-23页

作者： Jundan Yu Peishan Qiu Jingwen Ai Bo Liu Guan-Zhu Han Fan Zhu Wenhong Zhang Jie Cui Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response National Medical Center for Infectious Diseases Huashan Hospital Shanghai Medical College Fudan University CAS Key laboratory of Molecular virology &immunology Shanghai Institute of Immunity and Infection Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai Huashen Institute of Microbes and Infections College of Life Sciences Nanjing Normal University State Key laboratory of virology and Department of Medical Microbiology School of Basic Medical SciencesWuhan University The Institute of Infection and Health Research Fudan University Key laboratory of Medical Molecular virology(MOE/MOH) Shanghai Medical CollegeFudan University laboratory for Marine Biology and Biotechnology Qingdao Marine Science and Technology Center

Endogenous retroviruses (ERVs), the remnants of ancient retrovirus infections, constitute approximately 8% of the human genome and play important roles in human evolution, development,and diseases. Multiple drugs, such as DNA methyltransferase inhibitors and lysine-specific histone demethylase 1inhibitors, reactivate ERVs, induce viral mimicry and trigger innate immune responses to enhance tumor immunogenicity.

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C1QTNF5 is a novel attachment factor that facilitates the entry of influenza A virus

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Virologica Sinica 2024年第2期39卷 277-289页

作者： Lei Yu Xinjin Liu Xiaoqin Wei Junrui Ren Xueyun Wang Shuwen Wu Ke Lan State Key laboratory of virology Medical Research InstituteCollege of Life SciencesWuhan UniversityWuhan430072China Frontier Science Center for immunology and Metabolism Wuhan UniversityWuhan430072China Taikang Center for Life and Medical Sciences Wuhan UniversityWuhan430072China

Influenza A virus(IAV)binds sialic acid receptors on the cell surface to enter the host cells,which is the key step in initiating infection,transmission and *** the factors that contribute to the highly efficient entry of IAV into human cells will help elucidate the mechanism of viral entry and pathogenicity,and provide new targets for *** the present study,we reported a novel membrane protein,C1QTNF5,which binds to the hemagglutinin protein of IAV and promotes IAV infection in vitro and in *** found that the HA1 region of IAV hemagglutinin is critical for the interaction with C1QTNF5 protein,and C1QTNF5 interacts with hemagglutinin mainly through its N-terminus(1–103 aa).In addition,we further demonstrated that overexpression of C1QTNF5 promotes IAV entry,while blocking the interaction between C1QTNF5 and IAV hemagglutinin greatly inhibits viral ***,C1QTNF5 does not function as a receptor to mediate IAV infection in sialic acid-deficient CHO-Lec2 cells,but promotes IAV to attach to these cells,suggesting that C1QTNF5 is an important attachment factor for *** work reveals C1QTNF5 as a novel IAV attachment factor and provides a new perspective for antiviral strategies.

关键词： C1QTNF5 Influenza A virus Viral entry Hemagglutinin Attachment factor

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Turnip mosaic virus pathogenesis and host resistance mechanisms in Brassica

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Horticultural Plant Journal 2024年第4期10卷 947-960页

作者： Guanwei Wu Xinxin Fang Tianqi Yu Jianping Chen Fei Yan State Key laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Institute of Plant VirologyNingbo UniversityNingboZhejiang 315211China Key laboratory of Biotechnology in Plant Protection of MARA and Zhejiang Province Institute of Plant VirologyNingbo UniversityNingboZhejiang 315211China

Turnip mosaic virus(TuMV)is a devastating potyvirus pathogen that infects a wide variety of both cultivated and wild Brassicaceae *** urgently need more information and understanding of TuMV pathogenesis and the host responses involved in disease development in cruciferous *** displays great versatility in viral pathogenesis,especially in its replication and intercellular ***,in the coevolutionary arms races between TuMV and its hosts,the virus has evolved to co-opt host factors to facilitate its infection and counter host defense *** review mainly focuses on recent advances in understanding the viral factors that contribute to the TuMV infection cycle and the host resistance mechanism in ***,we propose some future research directions on TuMV pathogenesis and control strategies to design durable TuMV-resistant Brassica crops.

关键词： Turnip mosaic virus Brassica Resistance genes Host factors Infection biology

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Hsp90βis critical for the infection of severe fever with thrombocytopenia syndrome virus

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Virologica Sinica 2024年第1期39卷 113-122页

作者： Bo Wang Leike Zhang Fei Deng Zhihong Hu Manli Wang Jia Liu State Key laboratory of virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China The Third Affiliated Hospital of Guangzhou Medical University Guangzhou Medical UniversityGuangzhou511436China

Severe fever with thrombocytopenia syndrome(SFTS)caused by the SFTS virus(SFTSV)is an emerging disease in East Asia with a fatality rate of up to 30%.However,the viral-host interaction of SFTSV remains largely *** heat-shock protein 90(Hsp90)family consists of highly conserved chaperones that fold and remodel proteins and has a broad impact on the infection of many ***,we showed that Hsp90 is an important host factor involved in SFTSV ***90 inhibitors significantly reduced SFTSV replication,viral protein expression,and the formation of inclusion bodies consisting of nonstructural proteins(NSs).Among viral proteins,NSs appeared to be the most reduced when Hsp90 inhibitors were used,and further analysis showed that their translation was ***-immunoprecipitation of NSs with four isomers of Hsp90 showed that Hsp90βspecifically interacted with *** of Hsp90βexpression also inhibited replication of *** results suggest that Hsp90βplays a critical role during SFTSV infection and could be a potential target for the development of drugs against SFTS.

关键词： Severe fever with thrombocytopenia syndrome virus(SFTSV) Heat-shock protein 90 Hsp90β Host-virus interaction Nonstructural protein

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Single-domain antibodies as therapeutics for solid tumor treatment

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2854-2868页

作者： Mingkai Wang Tianlei Ying Yanling Wu MOE/NHC/CAMS Key laboratory of Medical Molecular virology School of Basic Medical SciencesDepartment of Pulmonary and Critical Care MedicineDepartment of Liver Surgery and TransplantationZhongshan HospitalFudan UniversityShanghai 200032China Shanghai Engineering Research Center for Synthetic immunology Shanghai 200032China

Single-domain antibodies(sdAbs),initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs,have emerged as a promising alternative to conventional therapeutic *** sdAbs have many superior physicochemical and pharmacological properties,including small size,good solubility and thermostability,easier accessible epitopes,and strong tissue ***,the inherent challenges associated with the animal origin of sdAbs limit their clinical *** recent years,various innovative humanization technologies,including complementarity-determining region(CDR)grafting or complete engineering of fully human sdAbs,have been developed to mitigate potential immunogenicity issues and enhance their *** review provides a comprehensive exploration of sdAbs,emphasizing their distinctive features and the progress in humanization *** addition,we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment,such as sdAbedrug conjugates,multispecific sdAbs,sdAb-based delivery systems,and sdAb-based cell therapy.

关键词： Single-domain antibody Nanobody Humanization Fully human singledomain antibody Solid tumor

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Mutual antagonism of mouse-adaptation mutations in HA and PA proteins on H9N2 virus replication

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Virologica Sinica 2024年第1期39卷 56-70页

作者： Liping Ma Huabin Zheng Xianliang Ke Rui Gui Zhongzi Yao Jiasong Xiong Quanjiao Chen CAS Key laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyChinese Academy of SciencesWuhan430207China Center for Biosafety Mega-Science Wuhan Institute of VirologyChinese Academy of SciencesWuhan430207China Hubei Jiangxia laboratory Wuhan430207China University of Chinese Academy of Sciences Beijing100049China

Avian H9N2 viruses have wide host range among the influenza A ***,knowledge of H9N2 mammalian adaptation is *** explore the molecular basis of the adaptation to mammals,we performed serial lung passaging of the H9N2 strain A/chicken/Hunan/8.27 YYGK3W3-OC/2018(3W3)in mice and identified six mutations in the hemagglutinin(HA)and polymerase acidic(PA)*** L226Q,T511I,and A528V of HA were responsible for enhanced pathogenicity and viral replication in mice;notably,HA-L226Q was the key *** T97I,I545V,and S594G of PA contributed to enhanced polymerase activity in mammalian cells and increased viral replication levels in vitro and in ***-T97I increased viral polymerase activity by accelerating the viral polymerase complex *** findings revealed that the viral replication was affected by the presence of PA-97I and/or PA-545V in combination with a triple-point HA ***,the double-and triple-point PA mutations demonstrated antagonistic effect on viral replication when combined with ***,any combination of PA mutations,along with double-point HA mutations,resulted in antagonistic effect on viral *** also observed antagonism in viral replication between PA-545V and PA-97I,as well as between HA-528V and *** findings demonstrated that several antagonistic mutations in HA and PA proteins affect viral replication,which may contribute to the H9N2 virus adaptation to mice and mammalian *** findings can potentially contribute to the monitoring of H9N2 field strains for assessing their potential risk in mammals.

关键词： Influenza Avirus(IAV) H9N2 HA PA Antagonism Mouse adaptation

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Emergence of highly pathogenic avian influenza A(H5N8)clade 2.3.4.4b viruses in grebes in Inner Mongolia and Ningxia,China,in 2021

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Journal of Integrative Agriculture 2024年第1期23卷 348-353页

作者： Qiuzi Xu Xinru Lü Yi Li Hua Luo Zhen Zhang Xiang Li Rongxiu Qin Qing An Fengyi Qu Zhenliang Zhao Chengbo Zhang Weidong Wang Yuecheng Li Yajun Wang Xiangwei Zeng Zhijun Hou Jingqiang Ren Yulong Wang Yanbing Li Hongliang Chai College of Wildlife and Protected Area Northeast Forestry UniversityHarbin 150040China Harbin Veterinary Research Institute Chinese Academy of Agricultural SciencesHarbin 150040China Wenzhou Key laboratory for virology and immunology Institute of VirologyWenzhou UniversityWenzhou 325000China Ordos Forestry and Grassland Administration Ordos 017000China Monitoring Center for Terrestrial Wildlife Epidemic Diseases Yinchuan 750000China

Highly pathogenic avian influenza(HPAI)subtype H5Nx viruses have spread globally and are a major concern for poultry,wild birds,mammals,and even humans(de Vries et al.2015;Zeng et al.2022).The hemagglutinin(HA)genes of H5 subtype viruses have evolved into multiple clades and some of these clades have been further divided into subclades(Cui et al.2022).Clade 2.***.4.4H5N8 HPAI viruses(HPAIVs)have caused several waves of disease outbreaks in wild birds and domestic poultry(Wang et al.2022).

关键词： poultry Ningxia influenza

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