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.
Highlights
LY6E is a glycosylphosphatidylinositol-anchored, IFN-inducible protein that regulates T lymphocytes proliferation, differentiation, and development
We examined whether HIV-1 infection in human peripheral blood mononuclear cells (PBMCs) can induce type I IFN production and LY6E expression
We noted that the up-regulation of IFN-, LY6E, and ISG15 correlated with the expression of HIV-1 Gag in infected cells (Fig. 1E), suggesting that HIV infection likely triggers a type I response and, induces LY6E expression in activated human PBMCs
Summary
LY6E is a glycosylphosphatidylinositol-anchored, IFN-inducible protein that regulates T lymphocytes proliferation, differentiation, and development. We show that LY6E promotes HIV, type 1 (HIV-1) infection by enhancing viral entry and gene expression. 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. 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. In chronically infected individuals, HIV-1 viral load positively correlates with the expression of type I IFN and ISGs [4]. Lymphocyte antigen 6 complex, locus E (LY6E), known as thymic shared antigen 1 (TSA-1), stem cell antigen 2 (SCA-2), and retinoic acid-induced gene E (RIG-E), is an IFN-inducible protein belonging to the Ly-6/uPAR family, whose members share structural and functional similarities. A whole-genome analysis identified a SNP, rs2572886, in the LY6/uPAR family that is associated with susceptibility to HIV-1, possibly because of increased LY6E expression [23]
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