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Repeated semen exposure decreases cervicovaginal SIVmac251 infection in rhesus macaques. 2019
Shaheed A Abdulhaqq, and
Melween Martinez, and
Guobin Kang, and
Idia V Rodriguez, and
Stephanie M Nichols, and
David Beaumont, and
Jocelin Joseph, and
Livio Azzoni, and
Xiangfan Yin, and
Megan Wise, and
David Weiner, and
Qin Liu, and
Andrea Foulkes, and
Jan Münch, and
Frank Kirchhoff, and
Christos Coutifaris, and
Georgia D Tomaras, and
Carlos Sariol, and
Preston A Marx, and
Qingsheng Li, and
Edmundo N Kraiselburd, and
Luis J Montaner
The Wistar Institute, Philadelphia, PA, USA.
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.
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