Year: 2019
Type: article
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.
Source: Nature Communications
Authors: 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, Luis J. Montaner
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: U.S. Department of Health and Human Services, University of Pennsylvania, Philadelphia Foundation, University of Pennsylvania Health System, Deutsche Forschungsgemeinschaft, Universität Ulm, National Institutes of Health, Center for AIDS Research, University of Washington, NIH Office of the Director, National Cancer Institute, National Institute of Allergy and Infectious Diseases
Awards: G1195029094, G1214792496, G1236295021, Training in Vaccine & Immune Therapeutics, G1615006977, G1682389719, G1809925070, G1852790566, G196529359, G1992474544, G226574744, G2601572497, G337926387, G3504457557, Center For AIDS Research, G4495922382, G4654975765, Early Innate/IgA Anti-HIV/SIV Response in Exposed Uninfected, G6073241214, G6368729432, G7249733449, G7489913356, G7988121182, G899581311, G9000000688, G9000085015, G9000250626, Center for AIDS Research, Consolidated Basic Cancer Research Program, Caribbean Primate Research Center Program
OpenAlex ID: W2969257863