title: Increases in Endogenous or Exogenous Progestins Promote Virus-Target Cell Interactions within the Non-human Primate Female Reproductive Tract.
abstract: Currently, there are mounting data suggesting that HIV-1 acquisition in women can be affected by the use of certain hormonal contraceptives. However, in non-human primate models, endogenous or exogenous progestin-dominant states are shown to increase acquisition. To gain mechanistic insights into this increased acquisition, we studied how mucosal barrier function and CD4+ T-cell and CD68+ macrophage density and localization changed in the presence of natural progestins or after injection with high-dose DMPA. The presence of natural or injected progestins increased virus penetration of the columnar epithelium and the infiltration of susceptible cells into a thinned squamous epithelium of the vaginal vault, increasing the likelihood of potential virus interactions with target cells. These data suggest that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progestin levels.
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Carias
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Shannon A
authors.identifier: 0000-0002-9055-4941
authors.initials: SA
authors.lastname: Allen
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Fought
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kotnik Halavaty
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Meegan R
authors.initials: MR
authors.lastname: Anderson
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Jimenez
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Michael D
authors.initials: MD
authors.lastname: McRaven
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Casey J
authors.initials: CJ
authors.lastname: Gioia
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Tara R
authors.initials: TR
authors.lastname: Henning
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Ellen N
authors.identifier: 0000-0003-3819-0324
authors.initials: EN
authors.lastname: Kersh
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: James M
authors.initials: JM
authors.lastname: Smith
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Lara E
authors.initials: LE
authors.lastname: Pereira
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Katherine
authors.initials: K
authors.lastname: Butler
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: S Janet M
authors.initials: SJ
authors.lastname: McNicholl
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: R Michael
authors.initials: RM
authors.lastname: Hendry
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Patrick F
authors.identifier: 0000-0002-3868-7122
authors.initials: PF
authors.lastname: Kiser
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, United States of America.
authors.forename: Ronald S
authors.identifier: 0000-0002-6298-2391
authors.initials: RS
authors.lastname: Veazey
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hope
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002584:Cervix Uteri / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D003692:Delayed-Action Preparations; D005260:Female; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D007273:Injections, Intramuscular; D008213:Lymphocyte Activation / Q000187:drug effects; D008253:Macaca mulatta; D008254:Macaca nemestrina; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000627:therapeutic use; D008597:Menstrual Cycle; D009092:Mucous Membrane / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D011372:Progestins / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D014621:Vagina / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D003692:Delayed-Action Preparations; D011372:Progestins; D017258:Medroxyprogesterone Acetate