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DOI10.1073/pnas.2108631118
STING facilitates nuclear import of herpesvirus genome during infection
Hong Y.; Jeong H.; Park K.; Lee S.; Shim J.Y.; Kim H.; Song Y.; Park S.; Park H.Y.; Kim V.N.; Ahn K.
发表日期2021
ISSN0027-8424
卷号118期号:33
英文摘要Once inside the host cell, DNA viruses must overcome the physical barrier posed by the nuclear envelope to establish a successful infection. The mechanism underlying this process remains unclear. Here, we show that the herpesvirus exploits the immune adaptor stimulator of interferon genes (STING) to facilitate nuclear import of the viral genome. Following the entry of the viral capsid into the cell, STING binds the viral capsid, mediates capsid docking to the nuclear pore complex via physical interaction, and subsequently enables accumulation of the viral genome in the nucleus. Silencing STING in human cytomegalovirus (HCMV)-susceptible cells inhibited nuclear import of the viral genome and reduced the ensuing viral gene expression. Overexpressing STING increased the host cell's susceptibility to HCMV and herpes simplex virus 1 by improving the nuclear delivery of viral DNA at the early stage of infection. These observations suggest that the proviral activity of STING is conserved and exploited by the herpesvirus family. Intriguingly, in monocytes, which act as latent reservoirs of HCMV, STING deficiency negatively regulated the establishment of HCMV latency and reactivation. Our findings identify STING as a proviral host factor regulating latency and reactivation of herpesviruses. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Cell susceptibility; HCMV; Nuclear import; STING
语种英语
scopus关键词membrane protein; STING protein; unclassified drug; capsid protein; membrane protein; small interfering RNA; STING1 protein, human; virus DNA; Article; controlled study; gene expression; herpes virus infection; Herpesviridae; human; Human alphaherpesvirus 1; human cell; molecular docking; nonhuman; protein binding; protein expression; protein interaction; virus capsid; virus entry; virus genome; virus latency; virus reactivation; cell line; Cytomegalovirus; gene expression regulation; genetics; metabolism; physiology; RNA interference; virus genome; virus replication; Capsid Proteins; Cell Line; Cytomegalovirus; DNA, Viral; Gene Expression Regulation, Viral; Genome, Viral; Membrane Proteins; RNA Interference; RNA, Small Interfering; Virus Internalization; Virus Replication
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/251052
作者单位School of Biological Sciences, Seoul National University, Seoul, 08826, South Korea; Center for RNA Research, Institute for Basic Science, Seoul, 08826, South Korea; Department of Physics and Astronomy, Seoul National University, Seoul, 08826, South Korea
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GB/T 7714
Hong Y.,Jeong H.,Park K.,et al. STING facilitates nuclear import of herpesvirus genome during infection[J],2021,118(33).
APA Hong Y..,Jeong H..,Park K..,Lee S..,Shim J.Y..,...&Ahn K..(2021).STING facilitates nuclear import of herpesvirus genome during infection.Proceedings of the National Academy of Sciences of the United States of America,118(33).
MLA Hong Y.,et al."STING facilitates nuclear import of herpesvirus genome during infection".Proceedings of the National Academy of Sciences of the United States of America 118.33(2021).
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