Single-cell RNA sequencing(scRNA-seq)has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell resolution.This review summarizes the existing scRNA-seq technologies togethe...Single-cell RNA sequencing(scRNA-seq)has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell resolution.This review summarizes the existing scRNA-seq technologies together with their strengths and weaknesses.The applications of scRNA-seq in various virological studies are discussed in depth,which broaden the understanding of the immune atlas,host-virus interactions,and immune repertoire.scRNA-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.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
MicroRNAs(miRNAs) are a class of small noncoding RNAs that post-transcriptionally regulate the expression of many target genes via mRNA degradation or translation inhibition. Many studies have shown that miRNAs are in...MicroRNAs(miRNAs) are a class of small noncoding RNAs that post-transcriptionally regulate the expression of many target genes via mRNA degradation or translation inhibition. Many studies have shown that miRNAs are involved in the modulation of gene expression and replication of hepatitis B virus(HBV) and hepatitis C virus(HCV) and play a pivotal role in host-virus interactions. Increasing evidence also demonstrates that viral infection leads to alteration of the miRNA expression profile in hepatic tissues or circulation. The deregulated miRNAs participate in hepatocellular carcinoma(HCC)initiation and progression by functioning as oncogenes or tumor suppressor genes by targeting various genes involved in cancer-related signaling pathways. The distinct expression pattern of miRNAs may be a useful marker for the diagnosis and prognosis of virus-related diseases considering the limitation of currently used biomarkers. Moreover, the role of deregulated miRNA in host-virus interactions and HCC development suggested that miRNAs may serve as therapeutic targets or astools. In this review, we summarize the recent findings about the deregulation and the role of miRNAs during HBV/HCV infection and HCC development, and we discuss the possible mechanism of action of miRNAs in the pathogenesis of virus-related diseases. Furthermore, we discuss the potential of using miRNAs as markers for diagnosis and prognosis as well as therapeutic targets and drugs.展开更多
Hepatitis B virus(HBV)infection is a global public health problem that causes persistent liver diseases such as chronic hepatitis,cirrhosis,and hepatocellular carcinoma.A large amount of people die annually from HBV i...Hepatitis B virus(HBV)infection is a global public health problem that causes persistent liver diseases such as chronic hepatitis,cirrhosis,and hepatocellular carcinoma.A large amount of people die annually from HBV infection.However,the pathogenesises of the HBV-related diseases are ill defined and the therapeutic strategies for the diseases are less than optimum.The recently discovered microRNAs(miRNAs)are tiny noncoding RNAs that regulate gene expression primarily at the post-transcriptional level by binding to mRNAs.miRNAs contribute to a variety of physiological and pathological processes.A number of miRNAs have been found to play a pivotal role in the host-virus interaction including host-HBV interaction.Numerous studies have indicated that HBV infection could change the cellular miRNA expression patterns and different stages of HBV associated disease have displayed distinctive miRNA profiles.Furthermore,the differential expressed miRNAs have been found involved in the progression of HBV-related diseases,for instance some miRNAs are involved in liver tumorigenesis and tumor metastasis.Studies have also shown that the circulating miRNA in serum or plasma might be a very useful biomarker for the diagnosis and prognosis of HBV-related diseases.In addition,miRNA-based therapy strategies have attracted increasing attention,indicating a promising future in the treatment of HBV-related diseases.展开更多
Noncoding RNAs(ncRNAs) play important roles in many biological processes and provide materials for evolutionary adaptations beyond protein-coding genes, such as in the arms race between the host and pathogen. However,...Noncoding RNAs(ncRNAs) play important roles in many biological processes and provide materials for evolutionary adaptations beyond protein-coding genes, such as in the arms race between the host and pathogen. However, currently, a comprehensive high-resolution analysis of primate genomes that includes the latest annotated ncRNAs is not available. Here, we developed a computational pipeline to estimate the selections that act on noncoding regions based on comparisons with a large number of reference sequences in introns adjacent to the interested regions. Our method yields result comparable with those of the established codon-based method and phyloP method for coding genes;thus, it provides a holistic framework for estimating the selection on the entire genome. We further showed that fastevolving protein-coding genes and their corresponding 50 UTRs have a significantly lower frequency of the CpG dinucleotides than those evolving at an average pace, and these fast-evolving genes are enriched in the process of immunity and host defense. We also identified fast-evolving miRNAs with antiviral functions in cells. Our results provide a resource for high-resolution evolution analysis of the primate genomes.展开更多
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...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.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can give rise to different clinical manifestations that are directly related to viral tissue damage or indirectly induced by the antiviral immune re...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can give rise to different clinical manifestations that are directly related to viral tissue damage or indirectly induced by the antiviral immune response.Hyper-activation of the immune system in an attempt to eradicate the infection may trigger autoimmunity.Several immune-mediated disorders have been described in SARS-CoV-2-infected individuals.These include cutaneous rashes and vasculitis,autoimmune cytopenia,anti-phospholipid syndrome,central or peripheral neuropathy,myositis and myocarditis.On the other hand,rheumatic patients were reported to have similar coronavirus disease 2019(COVID-19)incidence,morbidity and mortality rates compared to general population.This opinion review will summarize the crucial immunologic steps which occur during SARSCoV-2-infection that may link autoimmunity to COVID-19 and provides an opportunity for further discussion regarding this association.展开更多
Background:The immune system of insects exerts fundamentally different antiviral mechanisms than mammals.MicroRNAs(miRNAs)play vital roles in developing insect antiviral immunity.MiRNAs expression profiles of insects ...Background:The immune system of insects exerts fundamentally different antiviral mechanisms than mammals.MicroRNAs(miRNAs)play vital roles in developing insect antiviral immunity.MiRNAs expression profiles of insects changed significantly during baculovirus infection.Methods:Differential expression profiles of miRNAs in Spodoptera frugiperda were monitored by next-generation sequencing(NGS)and RT-qPCR during Autographa californica multiple nucleopolyhedrovirus(AcMNPV)infection.The transcription levels of genes were detected by RT-qPCR.The 50%tissue culture infective dose(TCID_(50))endpoint dilution assay was used to determine the proliferation of progeny virus.Results:NGS revealed that 49 miRNAs were differentially expressed in Sf9 cells,and 10 of them were significantly up-or down-regulated.Though RT-qPCR analysis,we observed the similar trends for the expression patterns of significantly differentially expressed miRNAs from NGS.Moreover,the transcription levels of core genes,Exportin5,Dicer1,and Argonaute1,in miRNA biogenesis pathways were significantly increased after AcMNPV infection.For five selected miRNAs,miR-34-5p could regulate the proliferation of baculovirus progeny virus and energy metabolism.Conclusion:The miRNAs biogenesis pathway in Sf9 cells plays an important role and may be stimulated to resist AcMNPV infection.This work provides evidence for the molecular mechanism of baculovirus-insect interaction and offers novel ideas and directions for green pest control technology.展开更多
Hepatitis B virus (HBV) infection,a major public health problem,causes acute and chronic hepatitis that is often complicated by liver cirrhosis and hepatocellular carcinoma.The pathogenic mechanisms of HBV-related liv...Hepatitis B virus (HBV) infection,a major public health problem,causes acute and chronic hepatitis that is often complicated by liver cirrhosis and hepatocellular carcinoma.The pathogenic mechanisms of HBV-related liver disease are not well understood,and the current licensed therapies are not effective in permanently clearing virus from the circulation.In recent years,the role of micro-ribonucleic acids (miRNAs) in HBV infection has attracted great interest.Cellular miRNAs can influence HBV replication directly by binding to HBV transcripts and indirectly by targeting cellular factors relevant to the HBV life cycle.They are also involved in the regulation of cellular genes and signaling pathways that have critical roles in HBV pathogenesis.HBV infection,in turn,can trigger changes in cellular miRNA expression that are associated with distinctive miRNA expression profiles depending on the phase of liver disease.These alterations in miRNA expression have been linked to disease progression and hepatocarcinogenesis.We provide here an up to date review regarding the field of miRNAs and HBV interplay and highlight the potential utility of miRNAs as diagnostic biomarkers and therapeutic targets for the management of HBV-related liver disease.展开更多
The re-emergence of Zika virus(ZIKV) and its associated neonatal microcephaly and Guillain-Barré syndrome have led the World Health Organization to declare a global health emergency. Until today, many related stu...The re-emergence of Zika virus(ZIKV) and its associated neonatal microcephaly and Guillain-Barré syndrome have led the World Health Organization to declare a global health emergency. Until today, many related studies have successively reported the role of various viral proteins of ZIKVin the process of ZIKVinfection and pathogenicity. These studies have provided significant insights for the treatment and prevention of ZIKV infection. Here we review the current research advances in the functional characterization of the interactions between each ZIKV viral protein and its host factors.展开更多
It is generally accepted that human influenza viruses preferentially bind to cell-surface glycoproteins/ glycolipids containing sialic acids in α2,6-linkage; while avian and equine influenza viruses preferentially bi...It is generally accepted that human influenza viruses preferentially bind to cell-surface glycoproteins/ glycolipids containing sialic acids in α2,6-linkage; while avian and equine influenza viruses preferentially bind to those containing sialic acids in α2,3-linkage. Even though this generalized view is accurate for H3 subtype isolates, it may not be accurate and absolute for all subtypes of influenza A viruses and, therefore, needs to be reevaluated carefully and realistically. Some of the studies published in major scientific journals on the subject of tissue tropism of influenza viruses are inconsistent and caused confusion in the scientific community. One of the reasons for the inconsistency is that most studies were quantitative descriptions of sialic acid receptor distributions based on lectin or influenza virus immunohistochemistry results with limited numbers of stained cells. In addition, recent studies indicate that α2,3- and α2,6-linked sialic acids are not the sole receptors determining tissue and host tropism of influenza viruses. In fact, determinants for tissue and host tropism of human, avian and animal influenza viruses are more complex than what has been generally accepted. Other factors, such as glycan topology, concentration of invading viruses, local density of receptors, lipid raft microdomains, coreceptors or sialic acid-independent receptors, may also be important. To more efficiently control the global spread of pandemic influenza such as the current circulating influenza A H1N1, it is crucial to clarify the determinants for tissue and host tropism of influenza viruses through quantitative analysis of experimental results. In this review, I will comment on some conflicting issues related to tissue and host tropism of influenza viruses, discuss the importance of quantitative analysis of lectin and influenza virus immunohistochemistry results and point out directions for future studies in this area, which should lead to a better understanding of tissue and host tropism of influenza viruses.展开更多
基金supported by the National Key Research and Devel-opment Program of China(2021YFC2300202)the National Natural Science Foundation of China(U1902210,81871641,81972979,82172266,82241071,and 81902048)+1 种基金the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan(IDHT20190510)the Beijing Key Laboratory of Emerging In-fectious Diseases(DTKF202103).
文摘Single-cell RNA sequencing(scRNA-seq)has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell resolution.This review summarizes the existing scRNA-seq technologies together with their strengths and weaknesses.The applications of scRNA-seq in various virological studies are discussed in depth,which broaden the understanding of the immune atlas,host-virus interactions,and immune repertoire.scRNA-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.
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 National Natural Science Foundation of China,No.91029714,No.31071191,No.31270818 and No.31101000Natural Science Foundation of Tianjin,No.09JCZDJC17500 and No.12JCZDJC25100
文摘MicroRNAs(miRNAs) are a class of small noncoding RNAs that post-transcriptionally regulate the expression of many target genes via mRNA degradation or translation inhibition. Many studies have shown that miRNAs are involved in the modulation of gene expression and replication of hepatitis B virus(HBV) and hepatitis C virus(HCV) and play a pivotal role in host-virus interactions. Increasing evidence also demonstrates that viral infection leads to alteration of the miRNA expression profile in hepatic tissues or circulation. The deregulated miRNAs participate in hepatocellular carcinoma(HCC)initiation and progression by functioning as oncogenes or tumor suppressor genes by targeting various genes involved in cancer-related signaling pathways. The distinct expression pattern of miRNAs may be a useful marker for the diagnosis and prognosis of virus-related diseases considering the limitation of currently used biomarkers. Moreover, the role of deregulated miRNA in host-virus interactions and HCC development suggested that miRNAs may serve as therapeutic targets or astools. In this review, we summarize the recent findings about the deregulation and the role of miRNAs during HBV/HCV infection and HCC development, and we discuss the possible mechanism of action of miRNAs in the pathogenesis of virus-related diseases. Furthermore, we discuss the potential of using miRNAs as markers for diagnosis and prognosis as well as therapeutic targets and drugs.
基金Supported by The National Natural Science Foundation of China,No. 8127181012-5 state S and T Projects for infectious diseases,No. 2012ZX10002-007+1 种基金Doctoral Fund of Ministry of Education of China,No. 20120101110009the National Basic Research Program,No. 2013CB531405
文摘Hepatitis B virus(HBV)infection is a global public health problem that causes persistent liver diseases such as chronic hepatitis,cirrhosis,and hepatocellular carcinoma.A large amount of people die annually from HBV infection.However,the pathogenesises of the HBV-related diseases are ill defined and the therapeutic strategies for the diseases are less than optimum.The recently discovered microRNAs(miRNAs)are tiny noncoding RNAs that regulate gene expression primarily at the post-transcriptional level by binding to mRNAs.miRNAs contribute to a variety of physiological and pathological processes.A number of miRNAs have been found to play a pivotal role in the host-virus interaction including host-HBV interaction.Numerous studies have indicated that HBV infection could change the cellular miRNA expression patterns and different stages of HBV associated disease have displayed distinctive miRNA profiles.Furthermore,the differential expressed miRNAs have been found involved in the progression of HBV-related diseases,for instance some miRNAs are involved in liver tumorigenesis and tumor metastasis.Studies have also shown that the circulating miRNA in serum or plasma might be a very useful biomarker for the diagnosis and prognosis of HBV-related diseases.In addition,miRNA-based therapy strategies have attracted increasing attention,indicating a promising future in the treatment of HBV-related diseases.
基金supported by the National Natural Science Foundation of China (Grant No. 31670777)the China National Funds for Distinguished Young Scientists (Grant No. 31722030)+2 种基金the Beijing Advanced Innovation Center for Structural Biology to X.T.the Tsinghua-Peking Joint Center for Life Sciences (Grant No. 61020100119)the National Thousand Young Talents Program of China (Grant No. 042021011) to X.L.
文摘Noncoding RNAs(ncRNAs) play important roles in many biological processes and provide materials for evolutionary adaptations beyond protein-coding genes, such as in the arms race between the host and pathogen. However, currently, a comprehensive high-resolution analysis of primate genomes that includes the latest annotated ncRNAs is not available. Here, we developed a computational pipeline to estimate the selections that act on noncoding regions based on comparisons with a large number of reference sequences in introns adjacent to the interested regions. Our method yields result comparable with those of the established codon-based method and phyloP method for coding genes;thus, it provides a holistic framework for estimating the selection on the entire genome. We further showed that fastevolving protein-coding genes and their corresponding 50 UTRs have a significantly lower frequency of the CpG dinucleotides than those evolving at an average pace, and these fast-evolving genes are enriched in the process of immunity and host defense. We also identified fast-evolving miRNAs with antiviral functions in cells. Our results provide a resource for high-resolution evolution analysis of the primate genomes.
基金supported by grants from the National Natural Science Foundation of China(31900146)the key Biosafety Science and Technology Program of Hubei Jiangxia Laboratory(JXBS001)+1 种基金the Hubei Natural Science Foundation for Distinguished Young Scholars(2021CFA050)the Creative Research Group Program of Natural Science Foundation of Hubei Province(2022CFA021).
文摘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.
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can give rise to different clinical manifestations that are directly related to viral tissue damage or indirectly induced by the antiviral immune response.Hyper-activation of the immune system in an attempt to eradicate the infection may trigger autoimmunity.Several immune-mediated disorders have been described in SARS-CoV-2-infected individuals.These include cutaneous rashes and vasculitis,autoimmune cytopenia,anti-phospholipid syndrome,central or peripheral neuropathy,myositis and myocarditis.On the other hand,rheumatic patients were reported to have similar coronavirus disease 2019(COVID-19)incidence,morbidity and mortality rates compared to general population.This opinion review will summarize the crucial immunologic steps which occur during SARSCoV-2-infection that may link autoimmunity to COVID-19 and provides an opportunity for further discussion regarding this association.
基金funded by the Natural Science Foundation of Shanxi Province,Grant No.201801D121193the Central Government Guiding Local Science and Technology Development Fund Project,Grant No.YDZJSX2022A001.
文摘Background:The immune system of insects exerts fundamentally different antiviral mechanisms than mammals.MicroRNAs(miRNAs)play vital roles in developing insect antiviral immunity.MiRNAs expression profiles of insects changed significantly during baculovirus infection.Methods:Differential expression profiles of miRNAs in Spodoptera frugiperda were monitored by next-generation sequencing(NGS)and RT-qPCR during Autographa californica multiple nucleopolyhedrovirus(AcMNPV)infection.The transcription levels of genes were detected by RT-qPCR.The 50%tissue culture infective dose(TCID_(50))endpoint dilution assay was used to determine the proliferation of progeny virus.Results:NGS revealed that 49 miRNAs were differentially expressed in Sf9 cells,and 10 of them were significantly up-or down-regulated.Though RT-qPCR analysis,we observed the similar trends for the expression patterns of significantly differentially expressed miRNAs from NGS.Moreover,the transcription levels of core genes,Exportin5,Dicer1,and Argonaute1,in miRNA biogenesis pathways were significantly increased after AcMNPV infection.For five selected miRNAs,miR-34-5p could regulate the proliferation of baculovirus progeny virus and energy metabolism.Conclusion:The miRNAs biogenesis pathway in Sf9 cells plays an important role and may be stimulated to resist AcMNPV infection.This work provides evidence for the molecular mechanism of baculovirus-insect interaction and offers novel ideas and directions for green pest control technology.
文摘Hepatitis B virus (HBV) infection,a major public health problem,causes acute and chronic hepatitis that is often complicated by liver cirrhosis and hepatocellular carcinoma.The pathogenic mechanisms of HBV-related liver disease are not well understood,and the current licensed therapies are not effective in permanently clearing virus from the circulation.In recent years,the role of micro-ribonucleic acids (miRNAs) in HBV infection has attracted great interest.Cellular miRNAs can influence HBV replication directly by binding to HBV transcripts and indirectly by targeting cellular factors relevant to the HBV life cycle.They are also involved in the regulation of cellular genes and signaling pathways that have critical roles in HBV pathogenesis.HBV infection,in turn,can trigger changes in cellular miRNA expression that are associated with distinctive miRNA expression profiles depending on the phase of liver disease.These alterations in miRNA expression have been linked to disease progression and hepatocarcinogenesis.We provide here an up to date review regarding the field of miRNAs and HBV interplay and highlight the potential utility of miRNAs as diagnostic biomarkers and therapeutic targets for the management of HBV-related liver disease.
文摘The re-emergence of Zika virus(ZIKV) and its associated neonatal microcephaly and Guillain-Barré syndrome have led the World Health Organization to declare a global health emergency. Until today, many related studies have successively reported the role of various viral proteins of ZIKVin the process of ZIKVinfection and pathogenicity. These studies have provided significant insights for the treatment and prevention of ZIKV infection. Here we review the current research advances in the functional characterization of the interactions between each ZIKV viral protein and its host factors.
文摘It is generally accepted that human influenza viruses preferentially bind to cell-surface glycoproteins/ glycolipids containing sialic acids in α2,6-linkage; while avian and equine influenza viruses preferentially bind to those containing sialic acids in α2,3-linkage. Even though this generalized view is accurate for H3 subtype isolates, it may not be accurate and absolute for all subtypes of influenza A viruses and, therefore, needs to be reevaluated carefully and realistically. Some of the studies published in major scientific journals on the subject of tissue tropism of influenza viruses are inconsistent and caused confusion in the scientific community. One of the reasons for the inconsistency is that most studies were quantitative descriptions of sialic acid receptor distributions based on lectin or influenza virus immunohistochemistry results with limited numbers of stained cells. In addition, recent studies indicate that α2,3- and α2,6-linked sialic acids are not the sole receptors determining tissue and host tropism of influenza viruses. In fact, determinants for tissue and host tropism of human, avian and animal influenza viruses are more complex than what has been generally accepted. Other factors, such as glycan topology, concentration of invading viruses, local density of receptors, lipid raft microdomains, coreceptors or sialic acid-independent receptors, may also be important. To more efficiently control the global spread of pandemic influenza such as the current circulating influenza A H1N1, it is crucial to clarify the determinants for tissue and host tropism of influenza viruses through quantitative analysis of experimental results. In this review, I will comment on some conflicting issues related to tissue and host tropism of influenza viruses, discuss the importance of quantitative analysis of lectin and influenza virus immunohistochemistry results and point out directions for future studies in this area, which should lead to a better understanding of tissue and host tropism of influenza viruses.
