title: Progesterone augments cell susceptibility to HIV-1 and HIV-1/HSV-2 co-infections.
abstract: 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 this study, we used an in vitro cell culture system to study the effects of progesterone 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 (1411.2 pg/mL) compared with cells without progesterone treatment (993.1 pg/mL). Increased cell death was noted with HSV-2 co-infection and in 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 biomarkers of disease progression were explored. Progesterone upregulated inflammatory cytokines and chemokines conversely and downregulated anti-apoptotic Bcl-2 expression. Nuclear protein analysis by electrophoretic mobility shift assay showed the association of progesterone with progesterone response element (PRE), which may lead to downregulation 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.
authors.affiliation: Lab of Molecular VirologyDivision of Emerging Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA Viswanath.Ragupathy@fda.hhs.gov Indira.hewlett@fda.hhs.gov.
authors.forename: Viswanath
authors.initials: V
authors.lastname: Ragupathy
authors.affiliation: Lab of Molecular VirologyDivision of Emerging Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Wang
authors.initials: W
authors.lastname: Xue
authors.affiliation: Lab of Molecular VirologyDivision of Emerging Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Tan
authors.affiliation: Lab of Molecular VirologyDivision of Emerging Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Krishnakumar
authors.initials: K
authors.lastname: Devadas
authors.affiliation: Division of Viral ProductsCenter for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Lab of Molecular VirologyDivision of Emerging Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA Viswanath.Ragupathy@fda.hhs.gov Indira.hewlett@fda.hhs.gov.
authors.forename: Indira
authors.initials: I
authors.lastname: Hewlett
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D060085:Coinfection; D004198:Disease Susceptibility; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006561:Herpes Simplex / Q000235:genetics / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D011374:Progesterone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D020218:Response Elements; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011374:Progesterone
keywords: HIV/HSV-2; apoptosis; hormonal contraception; infectivity; progesterone