In human immunodeficiency virus type 1 (HIV-1) infected women, oral or injectable progesterone containing contraceptive pills may enhance HIV-1 acquisition in vivo and the mechanism by which this occurs is not fully understood. In developing countries Herpes simplex virus type-2 (HSV-2) co-infection has been shown to be a risk for increase of HIV-1 acquisition and, if co-infected women use progesterone pills, infections may increase several fold. In the present study we used an invitro cell culture system to study progesterone effects on HIV-1 replication and to explore the molecular mechanism of progesterone effects on infected cells. In our in-vitro model, CEMss cells (lymphoblastoid cell line) were infected with either HIV-1 alone or co-infected with HSV-2. HIV-1 viral load was measured with and without sex hormone treatment. Progesterone treated cells showed an increase in HIV-1 viral load (1411.2pg/mL) compared to cells without progesterone treatment (993.1pg/mL). Increased cell death noted with HSV-2 co-infection and progesterone treated cells. Similar observations were noted in peripheral blood mononuclear cells (PBMC) cells derived from three female donors. Progesterone treated cells also showed reduced antiviral efficacy. Inflammatory cytokines and associations with bio-markers of disease progression were explored. Progesterone up regulated inflammatory cytokines and chemokines con-versely, down-regulated anti-apoptotic Bcl-2 expression. Nuclear protein analysis by electrophoretic mobility shift assay showed association of progesterone with Progesterone Response Element (PRE), which may lead to down regulation of Bcl-2. These data indicate that progesterone treatment enhances HIV-1 replication in infected cells and co-infection with HSV-2 may further fuel this process.
Progesterone augments cell susceptibility to HIV-1 and HIV-1/HSV-2 co-infections.