title: Interferon-inducible LY6E Protein Promotes HIV-1 Infection.
abstract: LY6E is a glycosylphosphatidylinositol-anchored, IFN-inducible protein that regulates T lymphocytes proliferation, differentiation, and development. Single-nucleotide polymorphism rs2572886 in the LY6 family protein locus has been shown to associate with accelerated progression to AIDS. In this study, we show that LY6E promotes HIV, type 1 (HIV-1) infection by enhancing viral entry and gene expression. Knockdown of LY6E in human peripheral blood mononuclear, SupT1, and THP-1 cells diminishes HIV-1 replication. Virion-cell and cell-cell fusion experiments revealed that LY6E promotes membrane fusion of the viral entry step. Interestingly, we find that LTR-driven HIV-1 gene expression is also enhanced by LY6E, suggesting additional roles of LY6E in HIV-1 replication. HIV-1 infection induces LY6E expression in human peripheral blood mononuclear cells, concomitant with increased production of type I IFN and some classical IFN-stimulated genes. Altogether, our results demonstrate that IFN-inducible LY6E promotes HIV-1 entry and replication and highlight a positive regulatory role of IFN-induced proteins in HIV-1 infection. Our work emphasizes the complexity of IFN-mediated signaling in HIV-host interaction and AIDS pathogenesis.
authors.affiliation: From the Center for Retrovirus Research.|Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210.
authors.forename: Jingyou
authors.initials: J
authors.lastname: Yu
authors.affiliation: the McGill AIDS Centre, Lady Davis Institute, Montreal, Quebec H3T 1E2, Canada, and.|the Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.affiliation: From the Center for Retrovirus Research, liu.6244@osu.edu.|Center for Microbial Interface Biology, and.
authors.forename: Shan-Lu
authors.identifier: 0000-0003-1620-3817
authors.initials: SL
authors.lastname: Liu
mesh_terms: D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D015967:Gene Expression Regulation, Viral; D055785:Gene Knockdown Techniques; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007372:Interferons / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D000954:Antigens, Surface; D058851:GPI-Linked Proteins; C439870:LY6E protein, human; D007372:Interferons
keywords: HIV; IFN-stimulated genes; LY6E; gene expression; lymphocyte; membrane fusion; virus entry