HIV-1 transmission in the male genital tract.
HIV-1 transmission in the male genital tract.
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DOI：
10.1111/j.1600-0897.2010.00933.x
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发表时间：
2011-03-01
期刊：
影响因子：
--
通讯作者：
Bomsel, Morgane
中科院分区：
文献类型：
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作者：
Ganor, Yonatan;Bomsel, Morgane
HIV-1主要是性传播感染，覆盖生殖器粘膜的上皮表面是HIV-1的主要传播部位。尽管有报道称男性包皮环切术可以减少60%的男性感染HIV-1，但HIV-1在男性生殖器传播的最初机制仍然难以捉摸。我们建立了两种新的成人包皮上皮模型，允许通过粘膜极极化感染HIV-1感染细胞，这些细胞存在于所有向矢量化HIV-1的分泌物中或无细胞的HIV-1。有效的HIV-1传播发生在包皮内部（而非外部）极化暴露于高度感染HIV-1的单个核细胞（而非无细胞病毒）1小时后。HIV-1感染细胞与根尖包皮角化细胞形成病毒突触，导致HIV-1的极化出芽，并迅速被包皮内的朗格汉斯细胞（LCs）内化。反过来，LCs与t细胞形成结合物，从而转移HIV-1。hiv阴性男性的精液与hiv阳性女性的宫颈阴道分泌物混合在一起，这模拟了HIV-1在女性与男性的性传播过程中这些生殖器液体的体内混合物，减少了包皮上的HIV-1感染。我们的结果在细胞水平上合理化了包皮环切术对男性HIV-1获得的明显保护结果。
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.