The role of ferroportin on HIV-1 transcription and replication

This project was specifically designed to identify the role of ferroportin protein on HIV transcription and replication. Ferroportin is the only iron transporter found on cell membranes and it is thought to be involved in iron overload. Iron overload directly influences HIV-1 transcription and replication in vitro, but the influence of the ferroportin on HIV-1 pathogenesis in vitro is yet to be elucidated.;In this dissertation, experiments were designed to analyze the effects of these proteins (wild type ferroportin (WT) and a ferroportin mutant Q248H), on HIV-1 in vitro pathogenesis. The ferroportin Q248H mutant is unique to only Africans and African Americans and its influence on HIV-1 transcription and replication in vitro were analyzed.;In vitro studies were performed using ferroportin WT and ferroportin Q248H mutant constructs transfected into Human Endothelial Kidney cells (HEK 293T) cells to determine the effect of wild type and mutant Fpn-Q248H on HIV-1 transcription and replication. In addition human peripheral blood monocytes expressing WT ferroportin and ferroportin Q248H were isolated, differentiated and infected with VSVG-HIV-Luc virus to establish the role of ferroportin in HIV-1 transcription and replication in macrophages. Data obtained from these studies confirmed that ferroportin plays an inhibitory role in HIV-1 transcription and replication in 293T cells and macrophages. Mutant Fpn Q248H was found to inhibit HIV-1 replication and may have a protective effect in the African and African American population against HIV-1 infection. We also concluded that HIV-1 infection is increased in increased ferritin concentrations in vitro.