Interferon-inducible LY6E Protein Promotes HIV-1 Infection [Immunology]

LY6E is a glycosylphosphatidylinositol (GPI)-anchored, interferon (IFN)-inducible protein that regulates T lymphocytes proliferation, differentiation and development. Single nucleotide polymorphism rs2572886 in LY6-family protein locus has been shown to associate with accelerated progression to AIDS. In this study, we showed that LY6E promotes HIV-1 infection by enhancing viral entry and gene expression. Knockdown of LY6E in human PBMCs, 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 the 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 PBMCs, concomitant with increased production of type I IFN and some classical IFN-stimulated genes (ISGs). 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.

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