HIV-1 Transmission in the Male Genital Tract

Authors

  • Yonatan Ganor,

    1. Mucosal Entry of HIV-1 and Mucosal Immunity, Cell Biology and Host Pathogen Interactions Department, Cochin Institute, Université Paris Descartes, CNRS (UMR 8104), Paris, France
    2. INSERM, U1016, Paris, France
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  • Morgane Bomsel

    1. Mucosal Entry of HIV-1 and Mucosal Immunity, Cell Biology and Host Pathogen Interactions Department, Cochin Institute, Université Paris Descartes, CNRS (UMR 8104), Paris, France
    2. INSERM, U1016, Paris, France
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Morgane Bomsel, Cochin Institute, INSERM U1016, CNRS UMR8104, Paris Descartes University, 22 rue Me´chain, 75014 Paris France.
E-mail: morgane.bomsel@inserm.fr

Abstract

Citation Ganor Y, Bomsel M. HIV-1 transmission in the male genital tract. Am J Reprod Immunol 2011; 65: 284–291

HIV-1 is mainly a sexually transmitted infection, and epithelial surfaces covering genital mucosa are the primary site of HIV-1 transmission. Although male circumcision was reported to reduce male acquisition of HIV-1 by 60%, the initial mechanisms of HIV-1 transmission in the male genitals remain elusive. We established two novel models of the adult human foreskin epithelium that allowed for polarized infection via the mucosal pole with either HIV-1-infected cells that are present in all secretions vectorizing HIV-1 or cell-free HIV-1. Efficient HIV-1 transmission occurs following 1 hr of polarized exposure of the inner, but not outer, foreskin to mononuclear cells highly infected with HIV-1, but not to cell-free virus. HIV-1-infected cells form viral synapses with apical foreskin keratinocytes, leading to polarized budding of HIV-1, which is rapidly internalized by Langerhans cells (LCs) in the inner foreskin. In turn, LCs form conjugates with T-cells, thereby transferring HIV-1. Seminal plasma from HIV-negative men mixed with cervico-vaginal secretions from HIV-positive women, which mimics the in-vivo mixture of these genital fluids during woman-to-man HIV-1 sexual transmission, decreases HIV-1 infection at the foreskin. Our results rationalize at the cellular level the apparent protective outcome of circumcision against HIV-1 acquisition by men.

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