title: Viral attachment induces rapid recruitment of an innate immune sensor (TRIM5α) to the plasma membrane.
abstract: TRIM5α (tripartite motif 5α) acts as a pattern recognition receptor specific for the retrovirus capsid lattice and blocks infection by HIV-1 immediately after entry. However, the precise mechanisms underlying this rapid recognition of viral components remain elusive. Here, we analyzed the influence of viral exposure on TRIM5α. Total internal reflection fluorescence microscopy and lipid flotation assays revealed rapid recruitment of a TRIM5α subpopulation to the plasma membrane (PM) upon exposure to vesicular stomatitis virus-G-pseudotyped HIV-1 viral-like particles (VLPs), but not to envelope (Env)-less HIV-1 VLPs. TRIM5α signals were frequently colocalized with those of HIV-1 capsid at the PM. Exposure to HIV-1 Env-pseudotyped HIV-1 vectors also triggered translocation of endogenous TRIM5α to lipid microdomains within human T cells. Similarly, clustering of lipid microdomains by a glycosphingolipid stereoisomer resulted in rapid TRIM5α recruitment to the PM. Of note, recruitment of endogenous rhesus TRIM5α to the PM prior to HIV-1 infection significantly increased the potency of viral restriction. Our data therefore suggest the importance of TRIM5α recruitment to the PM for TRIM5α-mediated innate immune sensing and restriction of retroviral infection.
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Seiga
authors.initials: S
authors.lastname: Ohmine
authors.forename: Raman Deep
authors.initials: RD
authors.lastname: Singh
authors.forename: David L
authors.initials: DL
authors.lastname: Marks
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Meyer
authors.forename: Richard E
authors.initials: RE
authors.lastname: Pagano
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006028:Glycosphingolipids / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D008253:Macaca mulatta; D021962:Membrane Microdomains / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015202:Protein Engineering; D021381:Protein Transport / Q000187:drug effects / Q000276:immunology; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D019076:Transgenes / Q000235:genetics; D018116:Vesiculovirus / Q000502:physiology*; D053585:Virus Attachment / Q000187:drug effects; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D036022:Capsid Proteins; D006028:Glycosphingolipids; D009124:Muscle Proteins; D051192:Receptors, Pattern Recognition; C485888:TRIM54 protein, human; D054299:env Gene Products, Human Immunodeficiency Virus
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