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

PLoS Pathogens

Shannon A. Allen¹  Ann M. Carias¹  Casey J. Gioia¹  Maria L. Jimenez¹  Katarina Kotnik Halavaty¹  Thomas J. Hope¹  Michael D. McRaven¹  Meegan R. Anderson¹  Patrick F. Kiser¹  Angela J. Fought²  Ellen N. Kersh³  R. Michael Hendry³  James M. Smith³  S. Janet M. McNicholl³  Katherine Butler³  Tara R. Henning³  Lara E. Pereira³  Ronald S. Veazey⁴ 

[1] Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America;Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America;Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America;Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, United States of America

关键词: Macaque;    HIV-1;    Epithelium;    Rhesus monkeys;    Virions;    Menstrual cycle;    Mucus;    Vagina;   

DOI  :  10.1371/journal.ppat.1005885

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY