Repeated semen exposure decreases cervicovaginal SIVmac251 infection in rhesus macaques

Shaheed A. Abdulhaqq, Melween Martinez, Guobin Kang, Idia V. Rodriguez, Stephanie M. Nichols, David Beaumont, Jocelin Joseph, Livio Azzoni, Xiangfan Yin, Megan Wise, David Weiner, Qin Liu, Andrea Foulkes, Jan Münch, Frank Kirchhoff, Christos Coutifaris, Georgia D. Tomaras, Carlos Sariol, Preston A. Marx, Qingsheng LiEdmundo N. Kraiselburd, Luis J. Montaner

Research output: Contribution to journalArticle

Abstract

Semen is the vehicle for virion dissemination in the female reproductive tract (FRT) in male-to-female HIV transmission. Recent data suggests that higher frequency semen exposure is associated with activation of anti-HIV mechanisms in HIV negative sex workers. Here, we use a non-human primate (NHP) model to show that repeated vaginal exposure to semen significantly reduces subsequent infection by repeated low-dose vaginal SIVmac251 challenge. Repeated semen exposures result in lower CCR5 expression in circulating CD4+ T-cells, as well as higher expression of Mx1 (in correlation with IFNε expression) and FoxP3 in the cervicovaginal mucosa, and increased infiltration of CD4+ T-cells. Establishing in vivo evidence of competing effects of semen on transmission impacts our basic understanding of what factors may determine HIV infectivity in humans. Our results clearly indicate that repeated semen exposure can profoundly modulate the FRT microenvironment, paradoxically promoting host resistance against HIV acquisition.

Original languageEnglish (US)
Article number3753
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

    Fingerprint

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Abdulhaqq, S. A., Martinez, M., Kang, G., Rodriguez, I. V., Nichols, S. M., Beaumont, D., ... Montaner, L. J. (2019). Repeated semen exposure decreases cervicovaginal SIVmac251 infection in rhesus macaques. Nature communications, 10(1), [3753]. https://doi.org/10.1038/s41467-019-11814-5