Viral attachment induces rapid recruitment of an innate immune sensor (TRIM5α) to the plasma membrane.

TRIM5 alpha (tripartite motif 5 alpha) 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 TRIM5 alpha. Total internal reflection fluorescence microscopy and lipid flotation assays revealed rapid recruitment of a TRIM5 alpha 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. TRIM5 alpha 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 TRIM alpha a to lipid microdomains within human T cells. Similarly, clustering of lipid microdomains by a glycosphingolipid stereoisomer resulted in rapid TRIM5 alpha recruitment to the PM. Of note, recruitment of endogenous rhesus TRIM5a to the PM prior to HIV1 infection significantly increased the potency of viral restriction. Our data therefore suggest the importance of TRIM5 alpha recruitment to the PM for TRIM5 alpha-mediated innate immune sensing and restriction of retroviral infection. Copyright (C) 2013. Karger AG, Basel