Type I interferon: understanding its role in HIV pathogenesis and therapy

Despite over 30 years of research, the contribution of type I interferons (IFN-Is) to both the control of HIV replication and initiation of immunologic damage remains debated. In acute infection, IFN-Is, likely from plasmacytoid dendritic cells (pDCs), activate NK cells and upregulate restriction factors targeting virtually the entire HIV life cycle. In chronic infection, IFN-Is may also contribute to CD4 T cell loss and immune exhaustion. pDCs subsequently infiltrate lymphoid and mucosal tissues, and their circulating populations wane in chronic infection; IFN-I may be produced by other cells. Data from nonhuman primates indicate prompt IFN-I signaling is critical in acute infection. Whereas some studies showed IFN-I administration without combination antiretroviral therapy (cART) is beneficial, others suggest that stimulating or blocking IFN-I signaling in chronic ART-suppressed HIV infection has had positive results. Here, we describe the history of HIV and IFN-I, IFN-I's sources, IFN-I's effects on HIV control and host defense, and recent interventional studies in SIV and HIV infection.