Antiviral response and HIV-1 inhibition in sickle cell disease

Sickle cell disease (SCD) is characterized by hemolysis, vaso-occlusion, and ischemia. HIV-1 infection was previously shown to be suppressed in SCD PBMCs. Here, we report that HIV-1 suppression is attributed to the increased expression of iron, hypoxia, and interferon-induced innate antiviral factors. Inhibition of upregulated antiviral genes, HMOX-1, CDKN1A, and CH25H, increased HIV-1 replication in SCD PBMCs, suggesting their critical role in HIV-1 suppression. Levels of IFN-β were elevated in SCD patients. Sickle cell hemoglobin (HbS) treatment of THP-1-derived and primary monocyte-derived macrophages induced production of IFN-β, upregulated antiviral gene expression, and suppressed HIV-1 infection. Infection with mouse-adapted EcoHIV was suppressed in the SCD mice that also exhibited elevated levels of antiviral restriction factors. Our findings suggest that hemolysis and release of HbS leads to the induction of IFN-β production, induction of cellular antiviral state by the expression of iron and IFN-driven factors, and suppression of HIV-1 infection. [Display omitted] •Ex vivo HIV-1 inhibition in SCD PBMCs is mediated by innate antiviral response•Innate antiviral factors in SCD PBMCs are activated by hemolysis and IFN-β signaling•HbS induces production of IFN-β and suppresses HIV-1 infection•EcoHIV infection is suppressed in the SCD mice Virology; Hematology