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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

Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion

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Protein & Cell 2024年第6期15卷 403-418页

作者： Song Xue Yuru Han Fan Wu Qiao Wang Key laboratory of medical molecular virology (MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecurityShanghai Frontiers Science Center of Pathogenic Microorganisms and InfectionSchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles.Point mutations,particularly those within the receptor binding domain(RBD)of SARS-CoV-2 spike(S)protein,lead to the functional alteration in both receptor engagement and monoclonal antibody(mAb)recognition.Here,we review the data of the RBD point mutations possessed by major SARS-CoV-2 variants and discuss their individual effects on ACE2 affinity and immune evasion.Many single amino acid substitutions within RBD epitopes crucial for the antibody evasion capacity may conversely weaken ACE2 binding affinity.However,this weakened effect could be largely compensated by specific epistatic mutations,such as N501Y,thus maintaining the overall ACE2 affinity for the spike protein of all major variants.The predominant direction of SARS-CoV-2 evolution lies neither in promoting ACE2 affinity nor evading mAb neutralization but in maintaining a delicate balance between these two dimensions.Together,this review interprets how RBD mutations efficiently resist antibody neutralization and meanwhile how the affinity between ACE2 and spike protein is maintained,emphasizing the significance of comprehensive assessment of spike mutations.

关键词： ACE2 affinity maintained

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 unknown.The 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 viruses.Here,we showed that Hsp90 is an important host factor involved in SFTSV infection.Hsp90 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 affected.Co-immunoprecipitation of NSs with four isomers of Hsp90 showed that Hsp90βspecifically interacted with them.Knockdown of Hsp90βexpression also inhibited replication of SFTSV.These 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

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 concentrated.However,the mechanism of IBAG formation and the physiological function of IBAGs are unclear.Here,we found that the internal structures of RSV IBs are actual M2-1-free viral messenger ribonucleoprotein(mRNP)condensates formed by secondary LLPS.Mechanistically,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 separation.Furthermore,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 recruitment.Our 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

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

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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 ago.Among 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 schizophrenia.Additionally,neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with schizophrenia.Here,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 pathways.Clinical 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 controls.Further in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in schizophrenia.Studies 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 ferroptosis.Ongoing research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter activities.Moreover,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 ERVW-1.In 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

Classifying hepatitis B therapies with insights from covalently closed circular DNA dynamics

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Virologica Sinica 2024年第1期39卷 9-23页

作者： Jie-Li Hu Ai-Long Huang Key laboratory of molecular Biology on Infectious Diseases Ministry of EducationChongqing Medical UniversityChongqing400016China

The achievement of a functional cure for chronic hepatitis B(CHB)remains limited to a minority of patients treated with currently approved drugs.The primary objective in developing new anti-HBV drugs is to enhance the functional cure rates for CHB.A critical prerequisite for the functional cure of CHB is a substantial reduction,or even eradication of covalently closed circular DNA(cccDNA).Within this context,the changes in cccDNA levels during treatment become as a pivotal concern.We have previously analyzed the factors influencing cccDNA dynamics and introduced a preliminary classification of hepatitis B treatment strategies based on these dynamics.In this review,we employ a systems thinking perspective to elucidate the fundamental aspects of the HBV replication cycle and to rationalize the classification of treatment strategies according to their impact on the dynamic equilibrium of cccDNA.Building upon this foundation,we categorize current anti-HBV strategies into two distinct groups and advocate for their combined use to significantly reduce cccDNA levels within a well-defined timeframe.

关键词： Hepatitis B cccDNA Functional cure Dynamics Treatment Strategy

Interconnection of cellular autophagy and endosomal vesicle trafficking and its role in hepatitis B virus replication and release

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Virologica Sinica 2024年第1期39卷 24-30页

作者： Jia Li Yong Lin Xueyu Wang Mengji Lu Institute for virology University Hospital EssenUniversity of Duisburg-EssenEssen45122Germany Key laboratory of molecular Biology of Infectious Diseases(Chinese Ministry of Education) Chongqing Medical UniversityChongqing400016China The Key laboratory for Diagnosis and Treatment of Infectious Diseases The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310000China

Hepatitis B virus(HBV)produces and releases various particle types,including complete virions,subviral particles with envelope proteins,and naked capsids.Recent studies demonstrate that HBV exploits distinct intracellular membrane trafficking pathways,including the endosomal vesicle trafficking and autophagy pathway,to assemble and release viral and subviral particles.Herein,we summarize the findings about the distinct roles of autophagy and endosomal membrane trafficking and the interaction of both pathways in HBV replication,assembly,and release.

关键词： Amphisome Autophagy Endosomal vesicle Hepatitis B virus(HBV)

Viromes of Haemaphysalis longicornis reveal different viral abundance and diversity in free and engorged ticks

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Virologica Sinica 2024年第2期39卷 194-204页

作者： Jian Xiao Xuan Yao Xuhua Guan Jinfeng Xiong Yaohui Fang Jingyuan Zhang You Zhang Abulimiti Moming Zhengyuan Su Jiayin Jin Yingying Ge Jun Wang Zhaojun Fan Shuang Tang Shu Shen Fei Deng Key laboratory of virology and Biosafety and National Virus Resource Center Wuhan Institute of VirologyChinese Academy of SciencesWuhan430071China Hubei Provincial Center for Disease Control and Prevention Wuhan430070China University of Chinese Academy of Sciences Beijing101408China Hubei Jiangxia laboratory Wuhan430200China Xinjiang Key laboratory of Vector-borne Infectious Diseases Urumqi830002China Current address:Department of medical laboratory The Second Affiliated HospitalHainan Medical UniversityHaikou57000China

Haemaphysalis longicornis ticks,commonly found in East Asia,can transmit various pathogenic viruses,includingthe severe fever with thrombocytopenia syndrome virus(SFTSV)that has caused febrile diseases among humansin Hubei Province.However,understanding of the viromes of H.longicornis was limited,and the prevalence ofviruses among H.longicornis ticks in Hubei was not well clarified.This study investigates the viromes of bothengorged(fed)and free(unfed)H.longicornis ticks across three mountainous regions in Hubei Province from 2019to 2020.RNA-sequencing analysis identified viral sequences that were related to 39 reference viruses belonging tounclassified viruses and seven RNA viral families,namely Chuviridae,Nairoviridae,Orthomyxoviridae,Parvoviridae,Phenuiviridae,Rhabdoviridae,and Totiviridae.Viral abundance and diversity in these ticks were analysed,andphylogenetic characteristics of the Henan tick virus(HNTV),Dabieshan tick virus(DBSTV),Okutama tick virus(OKTV),and Jingmen tick virus(JMTV)were elucidated based on their full genomic sequences.Prevalenceanalysis demonstrated that DBSTV was the most common virus found in individual H.longicornis ticks(12.59%),followed by HNTV(0.35%),whereas JMTV and OKTV were not detected.These results improve our understanding of H.longicornis tick viromes in central China and highlight the role of tick feeding status and geographyin shaping the viral community.The findings of new viral strains and their potential impact on public health raisethe need to strengthen surveillance efforts for comprehensively assessing their spillover potentials.

关键词： Ticks Virome Haemaphysalis longicornis Phylogenetic analysis Viral abundance and diversity

Efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids in regulation of cytokines in autoimmune diseases a systematic review and Meta-analysis based on animal studies

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Journal of Traditional Chinese Medicine 2024年第3期44卷 417-426页

作者： ZHU Ruifang ZHANG Jun LYU Yaru CHEN Yulu HAN Shifan WANG Hongwei Key laboratory for molecular Diagnosis and Treatment of Hematologic Diseases Second Hospital of Shanxi Medical University Editorial Office First Hospital of Shanxi Medical University School of Nursing Shanxi Medical University

OBJECTIVE: To investigate the efficacy of substances containing 3 types of active ingredients-saponins,flavones, and alkaloids on experimental animals with autoimmune diseases(AIDs).METHODS: The protocol for this systematic review and Meta-analysis was prospectively registered with PROSPERO(CRD42023395741). Searches were conducted in the China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Journals, China Biomedical, Pub Med,Cochrane Library, and Embase databases to screen for animal studies investigating the therapeutic effects of saponins, flavones, or alkaloids on autoimmune diseases;consequently, corresponding data extraction tables were prepared. Systematic Review Centre for laboratory Animal Experimentation was used to assess the risk of methodological bias in the included literature. RevMan 5.4 was used for the Meta-analysis on the 8 serum cytokines.RESULTS: A total of 31 studies were included, all of which were randomized controlled studies. Meta-analysis indicated that substances rich in saponins, flavones, and alkaloids reduced serum levels of interleukin(IL)-1β[standardized mean difference(SMD) =-1.94, 95%confidence interval(CI)(-2.99,-0.90), P = 0.0003], IL-6 [SMD =-1.65, 95% CI(-2.33,-0.97,) P < 0.000 01],IL-17 [SMD =-2.41, 95% CI(-3.61,-1.20), P <0.0001], tumor necrosis factor(TNF)-α [SMD =-1.84, 95%CI(-2.61,-1.06), P < 0.0001], and interferon(IFN)-γ[SMD =-1.54, 95% CI(-2.43,-0.65), P = 0.0007], but increased serum levels of IL-4 [SMD = 1.30, 95% CI(0.15,2.44), P = 0.03) and IL-10 [SMD = 2.05, 95% CI(1.39,2.70), P < 0.000 01) in animal models. However, no significant regulatory effect of these three active components was observed on serum levels of IL-2 [SMD =-0.63, 95% CI(-1.82, 0.57), P = 0.30].CONCLUTIONS: Substances containing saponins,flavones, and alkaloids regulated the changes of immunerelated cytokines, it may be a novel dietary substance to relieve and control autoimmune diseases in the future.

关键词： Meta-analysis alkaloids autoimmune diseases flavones saponins system evaluation