title: Medroxyprogesterone Acetate Regulates HIV-1 Uptake and Transcytosis but Not Replication in Primary Genital Epithelial Cells, Resulting in Enhanced T-Cell Infection.
abstract: Although clinical and experimental evidence indicates that female sex hormones and hormonal contraceptives regulate susceptibility to human immunodeficiency virus type 1 (HIV-1) infection, the underlying mechanism remains unknown. Genital epithelial cells (GECs) are the first cells to encounter HIV during sexual transmission and their interaction with HIV may determine the outcome of exposure. This is the first report that HIV uptake by GECs increased significantly in the presence of the hormonal contraceptive medroxyprogesterone acetate (MPA) and progesterone and that uptake occurred primarily via endocytosis. No productive infection was detected, but endocytosed virus was released into apical and basolateral compartments. Significantly higher viral transcytosis was observed in the presence of MPA. In GEC and T-cell cocultures, maximum viral replication in T cells was observed in the presence of MPA, which also broadly upregulated chemokine production by GECs. These results suggest that MPA may play a significant role in regulating susceptibility to HIV.
authors.affiliation: Deptartment of Pathology and Molecular Medicine McMaster Immunology Research Centre, McMaster University, Hamilton.
authors.forename: Victor H
authors.initials: VH
authors.lastname: Ferreira
authors.affiliation: Deptartment of Pathology and Molecular Medicine McMaster Immunology Research Centre, McMaster University, Hamilton.
authors.forename: Sara
authors.initials: S
authors.lastname: Dizzell
authors.affiliation: Deptartment of Pathology and Molecular Medicine McMaster Immunology Research Centre, McMaster University, Hamilton.
authors.forename: Aisha
authors.initials: A
authors.lastname: Nazli
authors.affiliation: Deptartment of Pathology and Molecular Medicine McMaster Immunology Research Centre, McMaster University, Hamilton.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Kafka
authors.affiliation: Deptartment of Pathology and Molecular Medicine McMaster Immunology Research Centre, McMaster University, Hamilton.
authors.forename: Kristen
authors.initials: K
authors.lastname: Mueller
authors.affiliation: Deptartment of Pathology and Molecular Medicine McMaster Immunology Research Centre, McMaster University, Hamilton.
authors.forename: Philip V
authors.initials: PV
authors.lastname: Nguyen
authors.affiliation: Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec City, Canada.
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Tremblay
authors.affiliation: Department of Medical Genetics, University of Toronto.
authors.forename: Alan
authors.initials: A
authors.lastname: Cochrane
authors.affiliation: Deptartment of Pathology and Molecular Medicine McMaster Immunology Research Centre, McMaster University, Hamilton.
authors.forename: Charu
authors.initials: C
authors.lastname: Kaushic
mesh_terms: D002478:Cells, Cultured; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004705:Endocytosis; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology; D013601:T-Lymphocytes / Q000821:virology*; D015854:Up-Regulation; D014599:Uterus / Q000166:cytology; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D003271:Contraceptive Agents, Female; D016207:Cytokines; D011374:Progesterone; D017258:Medroxyprogesterone Acetate
keywords: HIV replication; HIV transmission; HIV-1; female sex hormones; genital epithelial cells; hormonal contraceptives; inflammation; medroxyprogesterone acetate; transcytosis