title: Cells infected with herpes simplex virus 1 export to uninfected cells exosomes containing STING, viral mRNAs, and microRNAs.
abstract: 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.
authors.affiliation: Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, Chicago, IL 60637.
authors.forename: Maria
authors.initials: M
authors.lastname: Kalamvoki
authors.affiliation: Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, Chicago, IL 60637.
authors.forename: Te
authors.initials: T
authors.lastname: Du
authors.affiliation: Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, Chicago, IL 60637 bernard.roizman@bsd.uchicago.edu.
authors.forename: Bernard
authors.initials: B
authors.lastname: Roizman
mesh_terms: D000818:Animals; D001692:Biological Transport; D002450:Cell Communication / Q000502:physiology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D060833:Cellular Microenvironment; D002522:Chlorocebus aethiops; D055354:Exosomes / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000821:virology*; D006561:Herpes Simplex / Q000635:transmission / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D060245:Tetraspanin 29 / Q000032:analysis; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology; D014771:Virion / Q000302:isolation & purification; D014774:Virulence; D014775:Virus Activation; D014779:Virus Replication; D000099197:STING Protein
chemical_list: D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D012367:RNA, Viral; D060245:Tetraspanin 29; D014764:Viral Proteins; C554869:CD9 protein, human; C532857:STING1 protein, human; D000099197:STING Protein
keywords: STING; exosomes; herpes simplex viruses; microRNAs; tetraspanins