HIV-1 infection in sickle cell disease and sickle cell trait: role of iron and innate response.

Sickle cell disease (SCD), an inherited hemoglobinopathy, affects primarily African Americans in the U.S.A. In addition, about 15% African Americans carry sickle cell trait (SCT). Despite the risk associated with blood transfusions, SCD patients have lower risk of acquiring HIV-1 infection. SCT individuals might also have some protection from HIV-1 infection. Here, we will review recent and previous studies with the focus on molecular mechanisms that might underlie and contribute to the protection of individuals with SCD and SCT from HIV-1 infection. As both of these conditions predispose to hemolysis, we will focus our discussion on the effects of systemic and intracellular iron on HIV-1 infection and progression. We will also review changes in iron metabolism and activation of innate antiviral responses in SCD and SCT and their effects on HIV-1 infection. Previous studies, including ours, showed that SCD might protect from HIV-1 infection. This protection is likely due to the upregulation of complex protein network in response to hemolysis, hypoxia and interferon signaling. These findings are important not only for HIV-1 field but also for SCD cure efforts as antiviral state of SCD patients may adversely affect lentivirus-based gene therapy efforts.