Membrane Protein OTOF Is a Type I Interferon-Induced Entry Inhibitor of HIV-1 in Macrophages

In humans, HIV-1 infection induces innate immune responses mediated mainly by type I interferon (IFN). Type I IFN restricts HIV-1 replication by upregulating the expression of IFN-stimulated genes with diverse anti-HIV properties. In this study, we report that the cell membrane protein otoferlin (OTOF) acts as a type I IFN-induced effector, inhibiting HIV-1 entry in myeloid lineage macrophages and dendritic cells (DCs). OTOF is significantly induced by type I IFN in macrophages and DCs but not in CD4(+) T lymphocytes. Silencing OTOF abrogates the IFN-mediated suppression of HIV-1 infection in macrophages and DCs. Moreover, OTOF overexpression exhibits anti-HIV activity in macrophages and CD4(+) T cells. Further evidence reveals that OTOF inhibits HIV-1 entry into target cells at the cell membrane. Collectively, OTOF is a downstream molecule induced by type I IFN to inhibit HIV-1 entry in macrophages; it is a new potential agent for the treatment of HIV infection.