HIV-1 transmission in the male genital tract.
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.
Mucosal Entry of HIV-1 and Mucosal Immunity, Cell Biology and Host Pathogen Interactions Department, Cochin Institute, Université Paris Descartes, CNRS-UMR 8104, 22 rue Méchain, Paris, France.
Yonatan
Y
Ganor
Morgane
M
Bomsel
D004847:Epithelial Cells / Q000821:virology; D005260:Female; D052816:Foreskin / Q000033:anatomy & histology* / Q000821:virology*; D005837:Genitalia, Male / Q000821:virology*; D015658:HIV Infections / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D007801:Langerhans Cells / Q000821:virology; D008297:Male; D009092:Mucous Membrane / Q000033:anatomy & histology / Q000821:virology; D012661:Semen; D014621:Vagina / Q000378:metabolism