Coxsackievirus A16(CVA16) is one of major pathogens of hand, foot and mouth disease(HFMD) in children. Long non-coding RNAs(Inc RNAs) have been implicated in various biological processes,but they have not been associa...Coxsackievirus A16(CVA16) is one of major pathogens of hand, foot and mouth disease(HFMD) in children. Long non-coding RNAs(Inc RNAs) have been implicated in various biological processes,but they have not been associated with CVA16 infection. In this study, we comprehensively characterized the landscape of Inc RNAs of normal and CVA16 infected rhabdomyosarcoma(RD)cells using RNA-Seq to investigate the functional relevance of Inc RNAs. We showed that a total of 760 Inc RNAs were upregulated and 1210 Inc RNAs were downregulated. Out of these dysregulated Inc RNAs, 43.64% were intergenic, 22.31% were sense, 15.89% were intronic, 8.67% were bidirectional, 5.59% were antisense, 3.85% were s RNA host Inc RNAs and 0.05% were enhancer. Six dysregulated Inc RNAs were validated by quantitative PCR assays and the secondary structures of these Inc RNAs were projected. Moreover, we conducted a bioinformatics analysis of an Inc RNAs(ENST00000602478) to elucidate the diversity of modification and functions of Inc RNAs. In summary, the current study compared the dysregulated Inc RNAs profile upon CVA16 challenge and illustrated the intricate relationship between coding and Inc RNAs transcripts. These results may not only provide a complete picture of transcription in CVA16 infected cells but also provide novel molecular targets for treatments of HFMD.展开更多
Apart from mediating viral entry,the function of the free HIV-1 envelope protein(gp120)has yet to be elucidated.Our group previously showed that EP2 derived from oneβ-strand in gp120 can form amyloid fibrils that inc...Apart from mediating viral entry,the function of the free HIV-1 envelope protein(gp120)has yet to be elucidated.Our group previously showed that EP2 derived from oneβ-strand in gp120 can form amyloid fibrils that increase HIV-1 infectivity.Importantly,gp120 contains~30β-strands.We examined whether gp120 might serve as a precursor protein for the proteolytic release of amyloidogenic fragments that form amyloid fibrils,thereby promoting viral infection.Peptide array scanning,enzyme degradation assays,and viral infection experiments in vitro confirmed that manyβ-stranded peptides derived from gp120 can indeed form amyloid fibrils that increase HIV-1 infectivity.These gp120-derived amyloidogenic peptides,or GAPs,which were confirmed to form amyloid fibrils,were termed gp120-derived enhancers of viral infection(GEVIs).GEVIs specifically capture HIV-1 virions and promote their attachment to target cells,thereby increasing HIV-1 infectivity.Different GAPs can cross-interact to form heterogeneous fibrils that retain the ability to increase HIV-1 infectivity.GEVIs even suppressed the antiviral activity of a panel of antiretroviral agents.Notably,endogenous GAPs and GEVIs were found in the lymphatic fluid,lymph nodes,and cerebrospinal fluid(CSF)of AIDS patients in vivo.Overall,gp120-derived amyloid fibrils might play a crucial role in the process of HIV-1 infectivity and thus represent novel targets for anti-HIV therapeutics.展开更多
基金supported by the National Natural Sciences Foundation of China(No.81171577,81371790,81371422 and 81171127)Major AIDS and Viral Hepatitis and Other Major Infectious Disease Prevention and Control project of China(2014ZX10001003)+1 种基金the Fundamental Research Funds for the Central Universities of Chinathe Translational Medical Research Fund of Wuhan University School of Medicine
文摘Coxsackievirus A16(CVA16) is one of major pathogens of hand, foot and mouth disease(HFMD) in children. Long non-coding RNAs(Inc RNAs) have been implicated in various biological processes,but they have not been associated with CVA16 infection. In this study, we comprehensively characterized the landscape of Inc RNAs of normal and CVA16 infected rhabdomyosarcoma(RD)cells using RNA-Seq to investigate the functional relevance of Inc RNAs. We showed that a total of 760 Inc RNAs were upregulated and 1210 Inc RNAs were downregulated. Out of these dysregulated Inc RNAs, 43.64% were intergenic, 22.31% were sense, 15.89% were intronic, 8.67% were bidirectional, 5.59% were antisense, 3.85% were s RNA host Inc RNAs and 0.05% were enhancer. Six dysregulated Inc RNAs were validated by quantitative PCR assays and the secondary structures of these Inc RNAs were projected. Moreover, we conducted a bioinformatics analysis of an Inc RNAs(ENST00000602478) to elucidate the diversity of modification and functions of Inc RNAs. In summary, the current study compared the dysregulated Inc RNAs profile upon CVA16 challenge and illustrated the intricate relationship between coding and Inc RNAs transcripts. These results may not only provide a complete picture of transcription in CVA16 infected cells but also provide novel molecular targets for treatments of HFMD.
基金supported by grants from the Natural Science Foundation of China(82072276 and 81772194 to ST,82073898 and 31370781 to SL,and 81630090 to SJ).
文摘Apart from mediating viral entry,the function of the free HIV-1 envelope protein(gp120)has yet to be elucidated.Our group previously showed that EP2 derived from oneβ-strand in gp120 can form amyloid fibrils that increase HIV-1 infectivity.Importantly,gp120 contains~30β-strands.We examined whether gp120 might serve as a precursor protein for the proteolytic release of amyloidogenic fragments that form amyloid fibrils,thereby promoting viral infection.Peptide array scanning,enzyme degradation assays,and viral infection experiments in vitro confirmed that manyβ-stranded peptides derived from gp120 can indeed form amyloid fibrils that increase HIV-1 infectivity.These gp120-derived amyloidogenic peptides,or GAPs,which were confirmed to form amyloid fibrils,were termed gp120-derived enhancers of viral infection(GEVIs).GEVIs specifically capture HIV-1 virions and promote their attachment to target cells,thereby increasing HIV-1 infectivity.Different GAPs can cross-interact to form heterogeneous fibrils that retain the ability to increase HIV-1 infectivity.GEVIs even suppressed the antiviral activity of a panel of antiretroviral agents.Notably,endogenous GAPs and GEVIs were found in the lymphatic fluid,lymph nodes,and cerebrospinal fluid(CSF)of AIDS patients in vivo.Overall,gp120-derived amyloid fibrils might play a crucial role in the process of HIV-1 infectivity and thus represent novel targets for anti-HIV therapeutics.
