The study of virus-host interactions has been significantly advanced using model organisms,with nematodes being a prominent example.Caenorhabditis elegans(C.elegans)nematodes have provided valuable insights into the m...The study of virus-host interactions has been significantly advanced using model organisms,with nematodes being a prominent example.Caenorhabditis elegans(C.elegans)nematodes have provided valuable insights into the mechanisms of viral infections,host defense strategies,and the development of antiviral therapies.With the discovery of natural viral pathogens of nematodes,Orsay virus,Le Blanc virus,Santeuil virus,and Mělník virus,the exploration of the virus-host interaction model based on nematodes has entered a new era.The virus-host interaction network consists of viruses,hosts,and the antagonistic effects of viruses on host immunity.The nematode virus-host interaction model is a concrete manifestation used to study the complex relationships among these three elements.Previous studies have indicated that during the entire process of nematode infection by viruses,antiviral RNA interference(RNAi)plays a crucial role.Additionally,the host’s innate immune responses,such as the antiviral-specific intracellular pathogen response(IPR)and certain signaling pathways homologous to those in humans,are particularly important in the natural immune and antiviral processes of nematodes.These processes are regulated by multiple genes in the host.The reverse genetics system for Orsay virus has been successfully developed to study viral gene function and virus-host interactions.Nematodes serve as simple host models for understanding RNA virus replication,related cellular components,and virus-host interaction mechanisms.These findings will likely contribute to the development of antiviral treatment strategies based on novel targets.展开更多
Viruses are extremely heterogeneous entities; the size and the nature of their genetic information, as well as the strategies employed to amplify and propagate their genomes, are highly variable. However, as obligator...Viruses are extremely heterogeneous entities; the size and the nature of their genetic information, as well as the strategies employed to amplify and propagate their genomes, are highly variable. However, as obligatory intracellular parasites, replication of all viruses relies on the host cell. Having co-evolved with their host for several million years, viruses have developed very sophisticated strategies to hijack cellular factors that promote virus uptake, replication, and spread. Identification of host cell factors(HCFs) required for these processes is a major challenge for researchers, but it enables the identification of new, highly selective targets for anti viral therapeutics. To this end, the establishment of platforms enabling genome-wide high-throughput RNA interference(HT-RNAi) screens has led to the identification of several key factors involved in the viral lifecycle. A number of genome-wide HT-RNAi screens have been performed for major human pathogens. These studies enable first inter-viral comparisons related to HCF requirements. Although several cellular functions appear to be uniformly required for the life cycle of most viruses tested(such as the proteasome and the Golgi-mediated secretory pathways), some factors, like the lipid kinase Phosphatidylinositol 4-kinase Ⅲα in the case of hepatitis C virus, are selectively required for individual viruses. However, despite the amount of data available, we are still far away from a comprehensive understanding of the interplay between viruses and host factors. Major limitations towards this goal are the low sensitivity and specificity of such screens, resulting in limited overlap between different screens performed with the same virus. This review focuses on how statistical and bioinformatic analysis methods applied to HTRNAi screens can help overcoming these issues thus increasing the reliability and impact of such studies.展开更多
Viral epidemics pose a serious threat to global public health,making it essential to explore virus-host interactions for uncovering the pathogenesis of viral diseases and developing effective antiviral strategies.Trad...Viral epidemics pose a serious threat to global public health,making it essential to explore virus-host interactions for uncovering the pathogenesis of viral diseases and developing effective antiviral strategies.Traditional in vitro cell infection models struggle to replicate physiological microenvironment,while animal infection models may encounter obstacles such as species gap,high-cost,and ethical issues.Additionally,potential heterogeneous infection outcomes are usually inaccessible by population-based experiments.Microfluidics,as an emerging interdisciplinary platform,has proven to be a powerful tool for inquiring virus-host interactions.In this review,conventional virological methods were introduced first and remarkable advantages of microfluidics in viral cell biology were highlighted.Next,the in-depth applications of microfluidics in analyzing heterogeneity of virus-host interplays,dynamic monitoring of events related to viral life cycle,and modeling of viral infectious diseases were fully elaborated from the perspective of single-cell chip,multi-cell culture chip and organ-on-a-chip(organ chip).Finally,the opportunities and challenges in developing robust microfluidic methods for virology were discussed.Overall,this review aims to provide an overview of microfluidic-based research on virus-host interaction and promote multidisciplinary collaborations for better understanding and responding to viral threats.展开更多
The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function,...The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.展开更多
In this review,the advantages and advances in applying high-throughput sequencing(HTS)in the management of viral diseases in citrus,along with some challenges,are discussed to provide perspectives on future prospects....In this review,the advantages and advances in applying high-throughput sequencing(HTS)in the management of viral diseases in citrus,along with some challenges,are discussed to provide perspectives on future prospects.Since the initial implementation of HTS in citrus virology,a substantial number of citrus viruses have been identified,with a notable increase in the last 7 years.The acquisition of viral genomes and various HTS-based omics analyses serve as crucial pillars for advancing research in the etiology,epidemiology,pathology,evolution,ecology,and biotechnology of citrus viruses.HTS has notably contributed to disease diagnosis,such as the diagnoses of concave gum and impietratura,as well as to the surveillance of new virus risks and the preparation of virus-free materials.However,certain inherent defects in HTS and coupled bioinformatics analysis,such as challenges with sequence assembly and the detection of viral dark matter,require improvement to enhance practical efficiency.In addition,the utilization of HTS for the systematic management of citrus viral diseases remains limited,and drawing insights from other virus-plant pathosystems while integrating emerging compatible techniques and ideas may broaden its specific applications.展开更多
Porcine reproductive and respiratory syndrome(PRRS),a highly infectious immunosuppressive disease caused by porcine reproductive and respiratory syndrome virus(PRRSV),has led to significant economic losses in the glob...Porcine reproductive and respiratory syndrome(PRRS),a highly infectious immunosuppressive disease caused by porcine reproductive and respiratory syndrome virus(PRRSV),has led to significant economic losses in the global swine industry.The complexity of preventing and controlling PRRS,compounded by the limited efficacy of current vaccines,underscores the urgent need to identify antiviral targets and develop effective therapeutics against PRRSV.From the perspective of virus-host interactions,the discovery of target molecules associated with PRRSV resistance offers a promising strategy for future disease management.In this study,we conduct a comprehensive proteomic analysis using data-independent acquisition(DIA)mode to investigate the host response throughout the acute phase of PRRSV infection.This approach provides critical insights into the regulation of host antiviral and immune pathways during acute infection,advancing our theoretical understanding of PRRSV-host interactions and host gene dynamics during this critical phase.Notably,we identified SCARB2,a major lysosomal membrane protein associated with cholesterol metabolism,as a potential regulator of PRRSV replication.These findings offer novel perspectives for the prevention and control of PRRSV,contributing to the development of targeted antiviral strategies.展开更多
Virus-encoding RNA-dependent RNA polymerase(RdRp)is essential for genome replication and gene transcription of human coronaviruses(HCoVs),including severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).We previo...Virus-encoding RNA-dependent RNA polymerase(RdRp)is essential for genome replication and gene transcription of human coronaviruses(HCoVs),including severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).We previously identified the interaction between the catalytic subunit NSP12 of SARS-CoV-2 RdRp and the host protein CREB-regulated transcription coactivator 3(CRTC3),a member of the CRTC family that regulates cyclic AMP response element-binding protein(CREB)-mediated transcriptional activation.Currently,the implication of CRTC3 in the pathogenesis of HCoVs is poorly understood.Herein,we demonstrated that CRTC3 attenuates RdRp activity and SARS-CoV-2 genome replication,therefore reducing the production of progeny viruses.The interaction of CRTC3 with NSP12 contributes to its inhibitory effect on RdRp activity.Furthermore,we expanded the suppressive effects of two other CRTC family members(CRTC1 and CRTC2)on the RdRp activities of lethal HCoVs,including SARS-CoV-2 and Middle East respiratory syndrome coronavirus(MERS-CoV),along with the CREB antagonization.Overall,our research suggests that CRTCs restrict the replication of HCoVs and are antagonized by CREB,which not only provides new insights into the replication regulation of HCoVs,but also offers important information for the development of anti-HCoV interventions.展开更多
甲型流感病毒(Influenza A viruses,IAVs)是危害人类和动物健康的主要病原之一,可通过基因重组和基因突变两种方式在自然界中不断进化,进而突破宿主屏障,扩大宿主范围,感染各种家禽、哺乳动物甚至人类,造成跨宿主传播.文章就影响IAVs跨...甲型流感病毒(Influenza A viruses,IAVs)是危害人类和动物健康的主要病原之一,可通过基因重组和基因突变两种方式在自然界中不断进化,进而突破宿主屏障,扩大宿主范围,感染各种家禽、哺乳动物甚至人类,造成跨宿主传播.文章就影响IAVs跨宿主传播因素的相关研究进行了综述,为IAVs的防控提供理论基础.展开更多
Cellular microRNAs(miRNAs) have been shown to modulate HCV infection via directly acting on the viral genome or indirectly through targeting the virus-associated host factors. Recently we generated a comprehensive map...Cellular microRNAs(miRNAs) have been shown to modulate HCV infection via directly acting on the viral genome or indirectly through targeting the virus-associated host factors. Recently we generated a comprehensive map of HCV–miRNA interactions through genome-wide miRNA functional screens and transcriptomics analyses. Many previously unappreciated cellular miRNAs were identified to be involved in HCV infection, including miR-135a, a human cancerrelated miRNA. In the present study, we investigated the role of miR-135a in regulating HCV life cycle and showed that it preferentially enhances viral genome replication. Bioinformatics-based integrative analyses and subsequent functional assays revealed three antiviral host factors, including receptor interacting serine/threonine kinase 2(RIPK2), myeloid differentiation primary response 88(MYD88), and C-X-C motif chemokine ligand 12(CXCL12), as bona fide targets of miR-135a. These genes have been shown to inhibit HCV infection at the RNA replication stage. Our data demonstrated that repression of key host restriction factors mediated the proviral effect of miR-135a on HCV propagation. In addition,miR-135a hepatic abundance is upregulated by HCV infection in both cultured hepatocytes and human liver, likely mediating a more favorable environment for viral replication and possibly contributing to HCV-induced liver malignancy.These results provide novel insights into HCV–host interactions and unveil molecular pathways linking miRNA biology to HCV pathogenesis.展开更多
Patients infected with the hepatitis C virus(HCV) are characterized by a high incidence of chronic infection, which results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The functional impairmen...Patients infected with the hepatitis C virus(HCV) are characterized by a high incidence of chronic infection, which results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The functional impairment of HCV-specific T cells is associated with the evolution of an acute infection to chronic hepatitis. While T cells are the important effector cells in adaptive immunity, natural killer(NK) cells are the critical effector cells in innate immunity to virus infections. The findings of recent studies on NK cells in hepatitis C suggest that NK cell responses are indeed important in each phase of HCV infection. In the early phase, NK cells are involved in protective immunity to HCV. The immune evasion strategies used by HCV may target NK cells and might contribute to the progression to chronic hepatitis C. NK cells may control HCV replication and modulate hepatic fibrosis in the chronic phase. Further investigations are, however, needed, because a considerable number of studies observed functional impairment of NK cells in chronic HCV infection. Interestingly, the enhanced NK cell responses during interferon-α-based therapy of chronic hepatitis C indicate successful treatment. In spite of the advances in research on NK cells in hepatitis C, establishment of more physiological HCV infection model systems is needed to settle unsolved controversies over the role and functional status of NK cells in HCV infection.展开更多
Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous vir...Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays, the impact of neutralizing responses for control of viral infection had been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses. In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodiesfor control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis.展开更多
Influenza A virus(IAV),responsible for seasonal epidemics and recurring pandemics,represents a global threat to public health.Given the risk of a potential IAV pandemic,it is increasingly important to better understan...Influenza A virus(IAV),responsible for seasonal epidemics and recurring pandemics,represents a global threat to public health.Given the risk of a potential IAV pandemic,it is increasingly important to better understand virushost interactions and develop new anti-viral strategies.Here,we reported nonmuscle myosin IIA(MYH9)-mediated regulation of IAV infection.MYH9 depletion caused a profound inhibition of IAV infection by reducing viral attachment and internalization in human lung epithelial cells.Surprisingly,overexpression of MYH9 also led to a significant reduction in viral productive infection.Interestingly,overexpression of MYH9 retained viral attachment,internalization,or uncoating,but suppressed the viral ribonucleoprotein(vRNP)activity in a minigenome system.Further analyses found that excess MYH9 might interrupt the formation of vRNP by interacting with the viral nucleoprotein(NP)and result in the reduction of the completed vRNP in the nucleus,thereby inhibiting subsequent viral RNA transcription and replication.Together,we discovered that MYH9 can interact with IAV NP protein and engage in the regulation of vRNP complexes,thereby involving viral replication.These findings enlighten new mechanistic insights into the complicated interface of host-IAV interactions,ultimately making it an attractive target for the generation of antiviral drugs.展开更多
Three crucial hurdles hinder studies on human cytomegalovirus(HCMV): strict species specificity, differences between in vivo and in vitro infection, and the complexity of gene regulation. Ever since the sequencing of ...Three crucial hurdles hinder studies on human cytomegalovirus(HCMV): strict species specificity, differences between in vivo and in vitro infection, and the complexity of gene regulation. Ever since the sequencing of the whole genome was first accomplished, functional studies on individual genes have been the mainstream in the CMV field. Gene regulation has therefore been elucidated in a more detailed fashion. However, viral gene regulation is largely controlled by both cellular and viral components. In other words, viral gene expression is determined by the virus–host interaction. Generally, cells respond to viral infection in a defensive pattern; at the same time, viruses try to counteract the cellular defense or else hide in the host(latency). Viruses evolve effective strategies against cellular defense in order to achieve replicative success. Whether or not they are successful, cellular defenses remain in the whole viral replication cycle: entry, immediate–early(IE) gene expression, early gene expression, DNA replication, late gene expression, and viral egress. Many viral strategies against cellular defense, and which occur in the immediate–early time of viral infection, have been documented. In this review, we will summarize the documented biological functions of IE1 and pp71 proteins, especially with regard to how they counteract cellular intrinsic defenses.展开更多
Coccolithophorid is unicellular marine microalgae with a global distribution in temperate and sub-temperate oceanic regions and has the ability to produce ＇the coccoliths＇. It is considered to be the second most pro...Coccolithophorid is unicellular marine microalgae with a global distribution in temperate and sub-temperate oceanic regions and has the ability to produce ＇the coccoliths＇. It is considered to be the second most productive calcifying organism on earth and becoming an important factor in the global carbonate cycle. Emiliania huxleyi is one of the only two bloom-forming coccolithophores and becomes a species crucial to the study of global biogeochemical cycles and climate modeling. Coccolithoviruse is a recently discovered group of viruses infecting the marine coceolithophorid E. huxleyi. They are a major cause of coceolithophore bloom termination, and DMSP concentration is increasing in the process of viral lysis. Phylogenetic evidences support that some genes are functional both in E. huxleyi and its virus （EhV）. Horizontal gene transfer （HGT） of multiple functionally coupled enzymes occurs in E. huxleyi and its DNA virus EhV has been confirmed, which contributes to the diversification and adaptation of plankton in the oceans and also critically regulates virus-host infection by allowing viruses to control host metabolic pathways for their repli- cation. Therefore, it is of particular interest to understand this host-virus interaction. On this issue, we have made a minireview of coeeolithoviruses focusing on the basic characteristics, phylogenesis, horizontal gene transfer and the interaction between the host and its viruses, as well as its important role in global biogeochemical cycling.展开更多
Dengue virus(DENV)infection is a worldwide public health threat.To date,the knowledge about the pathogenesis and progression of DENV infection is still limited.Combining global profiling based on proteomic analysis to...Dengue virus(DENV)infection is a worldwide public health threat.To date,the knowledge about the pathogenesis and progression of DENV infection is still limited.Combining global profiling based on proteomic analysis together with functional verification analysis is a powerful strategy to investigate the interplay between the virus and host cells.In the present study,quantitative proteomics has been applied to evaluate host responses(as indicated by altered proteins and modifications)in human cells(using K562 cell line)upon DENV-2 infection,as DENV-2 spreads most widely among all DENV serotypes.Comparative analysis was performed to define differentially expressed proteins in the infected cells compared to the mock-control,and it revealed critical pathogen-induced changes covering a broad spectrum of host cellular compartments and processes.We also discovered more dramatic changes(>20%,160 regulated phosphoproteins)in protein phosphorylation compared to protein expression(14%,321 regulated proteins).Most of these proteins/phosphoproteins were involved in transcription regulation,RNA splicing and processing,immune system,cellular response to stimulus,and macromolecule biosynthesis.Western blot analysis was also performed to confirm the proteomic data.Potential roles of these altered proteins were discussed.The present study provides valuable large-scale protein-related information for elucidating the functional emphasis of host cell proteins and their post-translational modifications in virus infection,and also provides insight and protein evidence for understanding the general pathogenesis and pathology of DENV.展开更多
Plus-strand RNA virus replication occurs in tight association with cytoplasmic host cell membranes. Both, viral and cellular factors cooperatively generate distinct organelle-like structures, designated viral replicat...Plus-strand RNA virus replication occurs in tight association with cytoplasmic host cell membranes. Both, viral and cellular factors cooperatively generate distinct organelle-like structures, designated viral replication factories. This compartmentalization allows coordination of the different steps of the viral replication cycle, highly efficient genome replication and protection of the viral RNA from cellular defense mechanisms. Electron tomography studies conducted during the last couple of years revealed the three dimensional structure of numerous plus-strand RNA virus replication compartments and highlight morphological analogies between different virus families. Based on the morphology of virusinduced membrane rearrangements, we propose two separate subclasses: the invaginated vesicle/spherule type and the double membrane vesicle type. This review discusses common themes and distinct differences in the architecture of plus-strand RNA virus-induced membrane alterations and summarizes recent progress that has been made in understanding the complex interplay between viral and co-opted cellular factors in biogenesis and maintenance of plus-strand RNA virus replication factories.展开更多
Plum pox virus（PPV）causes sharka-the most serious viral disease of stone fruit trees.PPV is wide spread in Europe and Mediterranean Basin,its incidence has been further approved in Asia and both Americas.Nine PPV st...Plum pox virus（PPV）causes sharka-the most serious viral disease of stone fruit trees.PPV is wide spread in Europe and Mediterranean Basin,its incidence has been further approved in Asia and both Americas.Nine PPV strains have been recognized until now（PPV-D,PPV-M,PPV-Rec,PPV-EA,PPV-C,PPV-T,PPV-W,PPV-CR,and PPV-An）,forming molecularly distinct entities,however,only partially differentiable by their biological or epidemiological properties.The most strict virus-host linkages under natural conditions have been detected for strains naturally infecting cherries（PPV-C and PPV-CR）.However,although less stringent but still clear host preference is observed also for three epidemiologically most important strains（PPV-D/plum/apricot,PPV-M/peach,and PPV-Rec/plum）.So far no genetic marker has been mapped in the PPV genome,which responsibility for the host specificity/preference could be explicitly demonstrated.In this review,we focus on the host preference of three major PPV strains as evidenced by analysis of an extensive dataset of PPV isolates of Slovak and world-wide origin.Together,we discuss several performed relevant experiments and further possible research procedures aimed to better understand the genetic determinants and mechanisms of the host preference of this potyvirus.展开更多
Flaviviruses,which include globally impactful pathogens,such as West Nile virus,yellow fever virus,Zika virus,Japanese encephalitis virus,and dengue virus,contribute significantly to human infections.Despite the ongoi...Flaviviruses,which include globally impactful pathogens,such as West Nile virus,yellow fever virus,Zika virus,Japanese encephalitis virus,and dengue virus,contribute significantly to human infections.Despite the ongoing emergence and resurgence of flavivirus-mediated pathogenesis,the absence of specific therapeutic options remains a challenge in the prevention and treatment of flaviviral infections.Through the intricate processes of fusion,transcription,replication,and maturation,the complex interplay of viral and host metabolic interactions affects pathophysiology.Crucial interactions involve metabolic molecules,such as amino acids,glucose,fatty acids,and nucleotides,each playing a pivotal role in the replication and maturation of flaviviruses.These viral-host metabolic molecular interactions hijack and modulate the molecular mechanisms of host metabolism.A comprehensive understanding of these intricate metabolic pathways offers valuable insights,potentially unveiling novel targets for therapeutic interventions against flaviviral pathogenesis.This review emphasizes promising avenues for the development of therapeutic agents that target specific metabolic molecules,such as amino acids,glucose,fatty acids,and nucleotides,which interact with flavivirus replication and are closely linked to the modulation of host metabolism.The clinical limitations of current drugs have prompted the development of new inhibitory strategies for flaviviruses based on an understanding of the molecular interactions between the virus and the host.展开更多
Crimean-Congo hemorrhagic fever virus(CCHFV)is a biosafety level-4(BSL-4)pathogen that causes Crimean-Congo hemorrhagic fever(CCHF)characterized by hemorrhagic manifestation,multiple organ failure and high mortality r...Crimean-Congo hemorrhagic fever virus(CCHFV)is a biosafety level-4(BSL-4)pathogen that causes Crimean-Congo hemorrhagic fever(CCHF)characterized by hemorrhagic manifestation,multiple organ failure and high mortality rate,posing great threat to public health.Despite the recently increasing research efforts on CCHFV,host cell responses associated with CCHFV infection remain to be further characterized.Here,to better understand the cellular response to CCHFV infection,we performed a transcriptomic analysis in human kidney HEK293 cells by high-throughput RNA sequencing(RNA-seq)technology.In total,496 differentially expressed genes(DEGs),including 361 up-regulated and 135 down-regulated genes,were identified in CCHFV-infected cells.These regulated genes were mainly involved in host processes including defense response to virus,response to stress,regulation of viral process,immune response,metabolism,stimulus,apoptosis and protein catabolic process.Therein,a significant up-regulation of type III interferon(IFN)signaling pathway as well as endoplasmic reticulum(ER)stress response was especially remarkable.Subsequently,representative DEGs from these processes were well validated by RT-qPCR,confirming the RNA-seq results and the typical regulation of IFN responses and ER stress by CCHFV.Furthermore,we demonstrate that not only type I but also type III IFNs(even at low dosages)have substantial anti-CCHFV activities.Collectively,the data may provide new and comprehensive insights into the virus-host interactions and particularly highlights the potential role of type III IFNs in restricting CCHFV,which may help inform further mechanistic delineation of the viral infection and development of anti-CCHFV strategies.展开更多
基金supported by National Undergraduate Training Programs for Innovation and Entrepreneurship of Ministry of Education,China.
文摘The study of virus-host interactions has been significantly advanced using model organisms,with nematodes being a prominent example.Caenorhabditis elegans(C.elegans)nematodes have provided valuable insights into the mechanisms of viral infections,host defense strategies,and the development of antiviral therapies.With the discovery of natural viral pathogens of nematodes,Orsay virus,Le Blanc virus,Santeuil virus,and Mělník virus,the exploration of the virus-host interaction model based on nematodes has entered a new era.The virus-host interaction network consists of viruses,hosts,and the antagonistic effects of viruses on host immunity.The nematode virus-host interaction model is a concrete manifestation used to study the complex relationships among these three elements.Previous studies have indicated that during the entire process of nematode infection by viruses,antiviral RNA interference(RNAi)plays a crucial role.Additionally,the host’s innate immune responses,such as the antiviral-specific intracellular pathogen response(IPR)and certain signaling pathways homologous to those in humans,are particularly important in the natural immune and antiviral processes of nematodes.These processes are regulated by multiple genes in the host.The reverse genetics system for Orsay virus has been successfully developed to study viral gene function and virus-host interactions.Nematodes serve as simple host models for understanding RNA virus replication,related cellular components,and virus-host interaction mechanisms.These findings will likely contribute to the development of antiviral treatment strategies based on novel targets.
文摘Viruses are extremely heterogeneous entities; the size and the nature of their genetic information, as well as the strategies employed to amplify and propagate their genomes, are highly variable. However, as obligatory intracellular parasites, replication of all viruses relies on the host cell. Having co-evolved with their host for several million years, viruses have developed very sophisticated strategies to hijack cellular factors that promote virus uptake, replication, and spread. Identification of host cell factors(HCFs) required for these processes is a major challenge for researchers, but it enables the identification of new, highly selective targets for anti viral therapeutics. To this end, the establishment of platforms enabling genome-wide high-throughput RNA interference(HT-RNAi) screens has led to the identification of several key factors involved in the viral lifecycle. A number of genome-wide HT-RNAi screens have been performed for major human pathogens. These studies enable first inter-viral comparisons related to HCF requirements. Although several cellular functions appear to be uniformly required for the life cycle of most viruses tested(such as the proteasome and the Golgi-mediated secretory pathways), some factors, like the lipid kinase Phosphatidylinositol 4-kinase Ⅲα in the case of hepatitis C virus, are selectively required for individual viruses. However, despite the amount of data available, we are still far away from a comprehensive understanding of the interplay between viruses and host factors. Major limitations towards this goal are the low sensitivity and specificity of such screens, resulting in limited overlap between different screens performed with the same virus. This review focuses on how statistical and bioinformatic analysis methods applied to HTRNAi screens can help overcoming these issues thus increasing the reliability and impact of such studies.
基金supported by the National Natural Science Foundation of China(Nos.22274118,22074107,and 81870359)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.22KJB320020)InnoHK funding(C2i)from Innovation&Technology Commission(ITC)of Hong Kong SAR Government。
文摘Viral epidemics pose a serious threat to global public health,making it essential to explore virus-host interactions for uncovering the pathogenesis of viral diseases and developing effective antiviral strategies.Traditional in vitro cell infection models struggle to replicate physiological microenvironment,while animal infection models may encounter obstacles such as species gap,high-cost,and ethical issues.Additionally,potential heterogeneous infection outcomes are usually inaccessible by population-based experiments.Microfluidics,as an emerging interdisciplinary platform,has proven to be a powerful tool for inquiring virus-host interactions.In this review,conventional virological methods were introduced first and remarkable advantages of microfluidics in viral cell biology were highlighted.Next,the in-depth applications of microfluidics in analyzing heterogeneity of virus-host interplays,dynamic monitoring of events related to viral life cycle,and modeling of viral infectious diseases were fully elaborated from the perspective of single-cell chip,multi-cell culture chip and organ-on-a-chip(organ chip).Finally,the opportunities and challenges in developing robust microfluidic methods for virology were discussed.Overall,this review aims to provide an overview of microfluidic-based research on virus-host interaction and promote multidisciplinary collaborations for better understanding and responding to viral threats.
基金supported by the National Natural Science Foundation of China(grant no.82370015).
文摘The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.
基金supported by National Natural Science Foundation of China(Grant Nos.32370005,32072389)Chongqing Science Funds for Distinguished Young Scientists(Grant No.CSTB2022NSCQ-JQX0027)+3 种基金Innovation Research 2035 Pilot Plan of Southwest University(Grant Nos.SWU-XDPY22002,SWUXDZD22002)Special Fund for Youth Team of Southwest University(Grant No.SWU-XJLJ202310)Chongqing Talents of Exceptional Young Talents Project(Grant No.cstc2022ycjh-bgzxm0143)Chongqing Municipal Training Program of Innovation and Entrepreneurship for Undergraduates(Grant No.S202310635160)。
文摘In this review,the advantages and advances in applying high-throughput sequencing(HTS)in the management of viral diseases in citrus,along with some challenges,are discussed to provide perspectives on future prospects.Since the initial implementation of HTS in citrus virology,a substantial number of citrus viruses have been identified,with a notable increase in the last 7 years.The acquisition of viral genomes and various HTS-based omics analyses serve as crucial pillars for advancing research in the etiology,epidemiology,pathology,evolution,ecology,and biotechnology of citrus viruses.HTS has notably contributed to disease diagnosis,such as the diagnoses of concave gum and impietratura,as well as to the surveillance of new virus risks and the preparation of virus-free materials.However,certain inherent defects in HTS and coupled bioinformatics analysis,such as challenges with sequence assembly and the detection of viral dark matter,require improvement to enhance practical efficiency.In addition,the utilization of HTS for the systematic management of citrus viral diseases remains limited,and drawing insights from other virus-plant pathosystems while integrating emerging compatible techniques and ideas may broaden its specific applications.
基金supported by the National Natural Science Foundation of China(grant no.:3217190296,82102755 and 32302887)Guangdong Basic and Applied Basic Research Foundation(grant no.:2023A1515012623 and 2019B1515210030)China Postdoctoral Science Foundation(grant no.:2021M703739)。
文摘Porcine reproductive and respiratory syndrome(PRRS),a highly infectious immunosuppressive disease caused by porcine reproductive and respiratory syndrome virus(PRRSV),has led to significant economic losses in the global swine industry.The complexity of preventing and controlling PRRS,compounded by the limited efficacy of current vaccines,underscores the urgent need to identify antiviral targets and develop effective therapeutics against PRRSV.From the perspective of virus-host interactions,the discovery of target molecules associated with PRRSV resistance offers a promising strategy for future disease management.In this study,we conduct a comprehensive proteomic analysis using data-independent acquisition(DIA)mode to investigate the host response throughout the acute phase of PRRSV infection.This approach provides critical insights into the regulation of host antiviral and immune pathways during acute infection,advancing our theoretical understanding of PRRSV-host interactions and host gene dynamics during this critical phase.Notably,we identified SCARB2,a major lysosomal membrane protein associated with cholesterol metabolism,as a potential regulator of PRRSV replication.These findings offer novel perspectives for the prevention and control of PRRSV,contributing to the development of targeted antiviral strategies.
基金supported by grants from the National Natural Science Foundation of China(32071236)the National Science Fund for Distinguished Young Scholars(32225001)+6 种基金the 1.3.5 Project for Disciplines Excellence of West China Hospital,Sichuan University(ZYGD23018)Key Science and Technology Research Projects in Key Areas of the Corps(2023AB053)the National Key Research and Development Program of China(2022YFC2303700)the Joint Project of Pengzhou People's Hospital with Southwest Medical University(2024PZXNYD02)Project funded by China Postdoctoral Science Foundation(2020M683304)Sichuan Science and Technology Support Project(2021YJ0502)Post-Doctor Research Project,West China Hospital,Sichuan University(2020HXBH082).
文摘Virus-encoding RNA-dependent RNA polymerase(RdRp)is essential for genome replication and gene transcription of human coronaviruses(HCoVs),including severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).We previously identified the interaction between the catalytic subunit NSP12 of SARS-CoV-2 RdRp and the host protein CREB-regulated transcription coactivator 3(CRTC3),a member of the CRTC family that regulates cyclic AMP response element-binding protein(CREB)-mediated transcriptional activation.Currently,the implication of CRTC3 in the pathogenesis of HCoVs is poorly understood.Herein,we demonstrated that CRTC3 attenuates RdRp activity and SARS-CoV-2 genome replication,therefore reducing the production of progeny viruses.The interaction of CRTC3 with NSP12 contributes to its inhibitory effect on RdRp activity.Furthermore,we expanded the suppressive effects of two other CRTC family members(CRTC1 and CRTC2)on the RdRp activities of lethal HCoVs,including SARS-CoV-2 and Middle East respiratory syndrome coronavirus(MERS-CoV),along with the CREB antagonization.Overall,our research suggests that CRTCs restrict the replication of HCoVs and are antagonized by CREB,which not only provides new insights into the replication regulation of HCoVs,but also offers important information for the development of anti-HCoV interventions.
文摘甲型流感病毒(Influenza A viruses,IAVs)是危害人类和动物健康的主要病原之一,可通过基因重组和基因突变两种方式在自然界中不断进化,进而突破宿主屏障,扩大宿主范围,感染各种家禽、哺乳动物甚至人类,造成跨宿主传播.文章就影响IAVs跨宿主传播因素的相关研究进行了综述,为IAVs的防控提供理论基础.
基金supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health
文摘Cellular microRNAs(miRNAs) have been shown to modulate HCV infection via directly acting on the viral genome or indirectly through targeting the virus-associated host factors. Recently we generated a comprehensive map of HCV–miRNA interactions through genome-wide miRNA functional screens and transcriptomics analyses. Many previously unappreciated cellular miRNAs were identified to be involved in HCV infection, including miR-135a, a human cancerrelated miRNA. In the present study, we investigated the role of miR-135a in regulating HCV life cycle and showed that it preferentially enhances viral genome replication. Bioinformatics-based integrative analyses and subsequent functional assays revealed three antiviral host factors, including receptor interacting serine/threonine kinase 2(RIPK2), myeloid differentiation primary response 88(MYD88), and C-X-C motif chemokine ligand 12(CXCL12), as bona fide targets of miR-135a. These genes have been shown to inhibit HCV infection at the RNA replication stage. Our data demonstrated that repression of key host restriction factors mediated the proviral effect of miR-135a on HCV propagation. In addition,miR-135a hepatic abundance is upregulated by HCV infection in both cultured hepatocytes and human liver, likely mediating a more favorable environment for viral replication and possibly contributing to HCV-induced liver malignancy.These results provide novel insights into HCV–host interactions and unveil molecular pathways linking miRNA biology to HCV pathogenesis.
基金Supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of ScienceICT&Future Planning+1 种基金No.2007-0056092No.2012R1A1A1012207 and No.2010-0027945
文摘Patients infected with the hepatitis C virus(HCV) are characterized by a high incidence of chronic infection, which results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The functional impairment of HCV-specific T cells is associated with the evolution of an acute infection to chronic hepatitis. While T cells are the important effector cells in adaptive immunity, natural killer(NK) cells are the critical effector cells in innate immunity to virus infections. The findings of recent studies on NK cells in hepatitis C suggest that NK cell responses are indeed important in each phase of HCV infection. In the early phase, NK cells are involved in protective immunity to HCV. The immune evasion strategies used by HCV may target NK cells and might contribute to the progression to chronic hepatitis C. NK cells may control HCV replication and modulate hepatic fibrosis in the chronic phase. Further investigations are, however, needed, because a considerable number of studies observed functional impairment of NK cells in chronic HCV infection. Interestingly, the enhanced NK cell responses during interferon-α-based therapy of chronic hepatitis C indicate successful treatment. In spite of the advances in research on NK cells in hepatitis C, establishment of more physiological HCV infection model systems is needed to settle unsolved controversies over the role and functional status of NK cells in HCV infection.
基金Inserm, France Université Louis Pasteur, France+3 种基金the European Union (Virgil Network of Excellence)the DeutscheForschungsgemeinschaft (Ba1417/11-1), Germanythe ANRchair of excellence program and ANRS, FranceInserm "PosteVert" research fellowship in the framework of Inserm EuropeanAssociated Laboratory Inserm U748-Department of Medicine Ⅱ,University of Freiburg, Germany
文摘Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays, the impact of neutralizing responses for control of viral infection had been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses. In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodiesfor control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis.
基金supported by the National Natural Science Foundation of China(82071788,81901598,81771704,and 82041015)National Key R&D Program of China(2022YFC2604100).
文摘Influenza A virus(IAV),responsible for seasonal epidemics and recurring pandemics,represents a global threat to public health.Given the risk of a potential IAV pandemic,it is increasingly important to better understand virushost interactions and develop new anti-viral strategies.Here,we reported nonmuscle myosin IIA(MYH9)-mediated regulation of IAV infection.MYH9 depletion caused a profound inhibition of IAV infection by reducing viral attachment and internalization in human lung epithelial cells.Surprisingly,overexpression of MYH9 also led to a significant reduction in viral productive infection.Interestingly,overexpression of MYH9 retained viral attachment,internalization,or uncoating,but suppressed the viral ribonucleoprotein(vRNP)activity in a minigenome system.Further analyses found that excess MYH9 might interrupt the formation of vRNP by interacting with the viral nucleoprotein(NP)and result in the reduction of the completed vRNP in the nucleus,thereby inhibiting subsequent viral RNA transcription and replication.Together,we discovered that MYH9 can interact with IAV NP protein and engage in the regulation of vRNP complexes,thereby involving viral replication.These findings enlighten new mechanistic insights into the complicated interface of host-IAV interactions,ultimately making it an attractive target for the generation of antiviral drugs.
基金supported by a pilot grant from the Research Center for Minority Institutes (RCMI) program (2G12RR003050-24/8G12MD007579-27) (Q.T.)an American Cancer Society grant (RSG-090289-01MPC) (Q.T)+1 种基金NIH/NIAID SC1AI112785 (Q.T.)the Ponce Health Sciences University/RCMI Publications Office (G12 RR003050/8G12MD007579-27)
文摘Three crucial hurdles hinder studies on human cytomegalovirus(HCMV): strict species specificity, differences between in vivo and in vitro infection, and the complexity of gene regulation. Ever since the sequencing of the whole genome was first accomplished, functional studies on individual genes have been the mainstream in the CMV field. Gene regulation has therefore been elucidated in a more detailed fashion. However, viral gene regulation is largely controlled by both cellular and viral components. In other words, viral gene expression is determined by the virus–host interaction. Generally, cells respond to viral infection in a defensive pattern; at the same time, viruses try to counteract the cellular defense or else hide in the host(latency). Viruses evolve effective strategies against cellular defense in order to achieve replicative success. Whether or not they are successful, cellular defenses remain in the whole viral replication cycle: entry, immediate–early(IE) gene expression, early gene expression, DNA replication, late gene expression, and viral egress. Many viral strategies against cellular defense, and which occur in the immediate–early time of viral infection, have been documented. In this review, we will summarize the documented biological functions of IE1 and pp71 proteins, especially with regard to how they counteract cellular intrinsic defenses.
基金funded by the Chinese Public Science and Technology Research Funds Projects of Ocean (No. 201305027)the National Natural Science Foundation of China (Nos. 40930847, 41376119)+1 种基金Funds of China Southern Oceano-graphic Research Center (No. 14GZP71NF35)Funds of Provincial Key Laboratory of Food Microbiology and Enzyme Engineering (No. M20140910)
文摘Coccolithophorid is unicellular marine microalgae with a global distribution in temperate and sub-temperate oceanic regions and has the ability to produce ＇the coccoliths＇. It is considered to be the second most productive calcifying organism on earth and becoming an important factor in the global carbonate cycle. Emiliania huxleyi is one of the only two bloom-forming coccolithophores and becomes a species crucial to the study of global biogeochemical cycles and climate modeling. Coccolithoviruse is a recently discovered group of viruses infecting the marine coceolithophorid E. huxleyi. They are a major cause of coceolithophore bloom termination, and DMSP concentration is increasing in the process of viral lysis. Phylogenetic evidences support that some genes are functional both in E. huxleyi and its virus （EhV）. Horizontal gene transfer （HGT） of multiple functionally coupled enzymes occurs in E. huxleyi and its DNA virus EhV has been confirmed, which contributes to the diversification and adaptation of plankton in the oceans and also critically regulates virus-host infection by allowing viruses to control host metabolic pathways for their repli- cation. Therefore, it is of particular interest to understand this host-virus interaction. On this issue, we have made a minireview of coeeolithoviruses focusing on the basic characteristics, phylogenesis, horizontal gene transfer and the interaction between the host and its viruses, as well as its important role in global biogeochemical cycling.
基金supported by the National Natural Science Foundation of China (31870827 to X.Zhao, 31670161 to X.Zhou., and 81873964 to Y.Q.)the Hubei Natural Science Foundation (2018CFB603 to X.Zhao)the Fundamental Research Funds for the Central Universities (2042018kf0247 to X.Zhao)
文摘Dengue virus(DENV)infection is a worldwide public health threat.To date,the knowledge about the pathogenesis and progression of DENV infection is still limited.Combining global profiling based on proteomic analysis together with functional verification analysis is a powerful strategy to investigate the interplay between the virus and host cells.In the present study,quantitative proteomics has been applied to evaluate host responses(as indicated by altered proteins and modifications)in human cells(using K562 cell line)upon DENV-2 infection,as DENV-2 spreads most widely among all DENV serotypes.Comparative analysis was performed to define differentially expressed proteins in the infected cells compared to the mock-control,and it revealed critical pathogen-induced changes covering a broad spectrum of host cellular compartments and processes.We also discovered more dramatic changes(>20%,160 regulated phosphoproteins)in protein phosphorylation compared to protein expression(14%,321 regulated proteins).Most of these proteins/phosphoproteins were involved in transcription regulation,RNA splicing and processing,immune system,cellular response to stimulus,and macromolecule biosynthesis.Western blot analysis was also performed to confirm the proteomic data.Potential roles of these altered proteins were discussed.The present study provides valuable large-scale protein-related information for elucidating the functional emphasis of host cell proteins and their post-translational modifications in virus infection,and also provides insight and protein evidence for understanding the general pathogenesis and pathology of DENV.
基金Supported by The DFG,SFB638,TP A5 and SFB/TRR83,TP 13
文摘Plus-strand RNA virus replication occurs in tight association with cytoplasmic host cell membranes. Both, viral and cellular factors cooperatively generate distinct organelle-like structures, designated viral replication factories. This compartmentalization allows coordination of the different steps of the viral replication cycle, highly efficient genome replication and protection of the viral RNA from cellular defense mechanisms. Electron tomography studies conducted during the last couple of years revealed the three dimensional structure of numerous plus-strand RNA virus replication compartments and highlight morphological analogies between different virus families. Based on the morphology of virusinduced membrane rearrangements, we propose two separate subclasses: the invaginated vesicle/spherule type and the double membrane vesicle type. This review discusses common themes and distinct differences in the architecture of plus-strand RNA virus-induced membrane alterations and summarizes recent progress that has been made in understanding the complex interplay between viral and co-opted cellular factors in biogenesis and maintenance of plus-strand RNA virus replication factories.
基金supported by the grants from the Scientific Grant Agency of Ministry of Education and the Slovak Academy of Sciences (2/0001/15)the Slovak Research and Development Agency (APVV-0174-12)
文摘Plum pox virus（PPV）causes sharka-the most serious viral disease of stone fruit trees.PPV is wide spread in Europe and Mediterranean Basin,its incidence has been further approved in Asia and both Americas.Nine PPV strains have been recognized until now（PPV-D,PPV-M,PPV-Rec,PPV-EA,PPV-C,PPV-T,PPV-W,PPV-CR,and PPV-An）,forming molecularly distinct entities,however,only partially differentiable by their biological or epidemiological properties.The most strict virus-host linkages under natural conditions have been detected for strains naturally infecting cherries（PPV-C and PPV-CR）.However,although less stringent but still clear host preference is observed also for three epidemiologically most important strains（PPV-D/plum/apricot,PPV-M/peach,and PPV-Rec/plum）.So far no genetic marker has been mapped in the PPV genome,which responsibility for the host specificity/preference could be explicitly demonstrated.In this review,we focus on the host preference of three major PPV strains as evidenced by analysis of an extensive dataset of PPV isolates of Slovak and world-wide origin.Together,we discuss several performed relevant experiments and further possible research procedures aimed to better understand the genetic determinants and mechanisms of the host preference of this potyvirus.
基金Supported by The South Korea Health Technology R and D Project through the South Korea Health Industry Development Institute,Funded by the Ministry of Health and Welfare,South Korea,No.HF20C0020.
文摘Flaviviruses,which include globally impactful pathogens,such as West Nile virus,yellow fever virus,Zika virus,Japanese encephalitis virus,and dengue virus,contribute significantly to human infections.Despite the ongoing emergence and resurgence of flavivirus-mediated pathogenesis,the absence of specific therapeutic options remains a challenge in the prevention and treatment of flaviviral infections.Through the intricate processes of fusion,transcription,replication,and maturation,the complex interplay of viral and host metabolic interactions affects pathophysiology.Crucial interactions involve metabolic molecules,such as amino acids,glucose,fatty acids,and nucleotides,each playing a pivotal role in the replication and maturation of flaviviruses.These viral-host metabolic molecular interactions hijack and modulate the molecular mechanisms of host metabolism.A comprehensive understanding of these intricate metabolic pathways offers valuable insights,potentially unveiling novel targets for therapeutic interventions against flaviviral pathogenesis.This review emphasizes promising avenues for the development of therapeutic agents that target specific metabolic molecules,such as amino acids,glucose,fatty acids,and nucleotides,which interact with flavivirus replication and are closely linked to the modulation of host metabolism.The clinical limitations of current drugs have prompted the development of new inhibitory strategies for flaviviruses based on an understanding of the molecular interactions between the virus and the host.
基金supported by the National Key Research and Development Program of China(2018YFA0507202)the National Natural Science Foundation of China(32170171,31870162,and 82161138003)the Youth Innovation Promotion Association of Chinese Academy of Sciences.
文摘Crimean-Congo hemorrhagic fever virus(CCHFV)is a biosafety level-4(BSL-4)pathogen that causes Crimean-Congo hemorrhagic fever(CCHF)characterized by hemorrhagic manifestation,multiple organ failure and high mortality rate,posing great threat to public health.Despite the recently increasing research efforts on CCHFV,host cell responses associated with CCHFV infection remain to be further characterized.Here,to better understand the cellular response to CCHFV infection,we performed a transcriptomic analysis in human kidney HEK293 cells by high-throughput RNA sequencing(RNA-seq)technology.In total,496 differentially expressed genes(DEGs),including 361 up-regulated and 135 down-regulated genes,were identified in CCHFV-infected cells.These regulated genes were mainly involved in host processes including defense response to virus,response to stress,regulation of viral process,immune response,metabolism,stimulus,apoptosis and protein catabolic process.Therein,a significant up-regulation of type III interferon(IFN)signaling pathway as well as endoplasmic reticulum(ER)stress response was especially remarkable.Subsequently,representative DEGs from these processes were well validated by RT-qPCR,confirming the RNA-seq results and the typical regulation of IFN responses and ER stress by CCHFV.Furthermore,we demonstrate that not only type I but also type III IFNs(even at low dosages)have substantial anti-CCHFV activities.Collectively,the data may provide new and comprehensive insights into the virus-host interactions and particularly highlights the potential role of type III IFNs in restricting CCHFV,which may help inform further mechanistic delineation of the viral infection and development of anti-CCHFV strategies.
