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 Li, Edmundo N. Kraiselburd and Luis J. Montaner ()
Additional contact information
Shaheed A. Abdulhaqq: The Wistar Institute
Melween Martinez: University of Puerto Rico (UPR)
Guobin Kang: School of Biological Sciences University of Nebraska
Idia V. Rodriguez: University of Puerto Rico (UPR)
Stephanie M. Nichols: University of Puerto Rico (UPR)
David Beaumont: Duke University
Jocelin Joseph: The Wistar Institute
Livio Azzoni: The Wistar Institute
Xiangfan Yin: The Wistar Institute
Megan Wise: The Wistar Institute
David Weiner: The Wistar Institute
Qin Liu: The Wistar Institute
Andrea Foulkes: Mount Holyoke College
Jan Münch: Ulm University Medical Center
Frank Kirchhoff: Ulm University Medical Center
Christos Coutifaris: University of Pennsylvania
Georgia D. Tomaras: Duke University
Carlos Sariol: University of Puerto Rico (UPR)
Preston A. Marx: Tulane University
Qingsheng Li: School of Biological Sciences University of Nebraska
Edmundo N. Kraiselburd: University of Puerto Rico (UPR)
Luis J. Montaner: The Wistar Institute

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11814-5

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