Increases in Endogenous or Exogenous Progestins Promote Virus-Target Cell Interactions within the Non-human Primate Female Reproductive Tract

Ann M. Carias, Shannon A. Allen, Angela J. Fought, Katarina Kotnik Halavaty, Meegan R. Anderson, Maria L. Jimenez, Michael D. McRaven, Casey J. Gioia, Tara R. Henning, Ellen N. Kersh, James M. Smith, Lara E. Pereira, Katherine Butler, S. Janet M. McNicholl, R. Michael Hendry, Patrick F. Kiser, Ronald S. Veazey, Thomas J. Hope*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Article numbere1005885
JournalPLoS pathogens
Volume12
Issue number9
DOIs
StatePublished - Sep 2016

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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