文章基本信息

标题：Cells infected with herpes simplex virus 1 export to uninfected cells exosomes containing STING, viral mRNAs, and microRNAs
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作者：Maria Kalamvoki ; Te Du ; Bernard Roizman 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：46
页码：E4991-E4996
DOI：10.1073/pnas.1419338111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe stimulator of IFN genes (STING) is an important innate immune response to infection by herpes simplex virus 1 (HSV-1). STING's impact may be deduced from the observation that HSV-1 replicates significantly better in normal immortalized cells depleted of STING. Nevertheless, published evidence shows that STING is stabilized by the virus in infected cells, and this report shows that STING is exported from infected cells in exosomes along with viral microRNAs (miRNAs) and mRNAs. Some miRNAs have been reported to suppress reactivation of latent virus. The results suggest that HSV-1 in special circumstances may control the spread of infection from cell to cell and support the hypothesis that HSV-1 controls its virulence to enable effective person-to-person transmission. STING (stimulator of IFN genes) activates the IFN-dependent innate immune response to infection on sensing the presence of DNA in cytosol. The quantity of STING accumulating in cultured cells varies; it is relatively high in some cell lines [e.g., HEp-2, human embryonic lung fibroblasts (HEL), and HeLa] and low in others (e.g., Vero cells). In a preceding publication we reported that STING was stable in four cell lines infected with herpes simplex virus 1 and that it was actively stabilized in at least two cell lines derived from human cancers. In this report we show that STING is exported from HEp-2 cells to Vero cells along with virions, viral mRNAs, microRNAs, and the exosome marker protein CD9. The virions and exosomes copurified. The quantity of STING and CD9 exported from one cell line to another was inoculum-size-dependent and reflected the levels of STING and CD9 accumulating in the cells in which the virus inoculum was made. The export of STING, an innate immune sensor, and of viral mRNAs whose major role may be in silencing viral genes in latently infected neurons, suggests that the virus has evolved mechanisms that curtail rather than foster the spread of infection under certain conditions.
关键词：herpes simplex viruses ; exosomes ; STING ; microRNAs ; tetraspanins