Exosomes as an early line of defense against HIV-1 infection

性接触是HIV-1传播的一种主要方式， 发生在男性和女性的异性接触中。因此，全世界约有1600万妇女 感染了HIV-1。异性性传播包括肛交和阴道性交; 与HIV-1阳性男性进行阴道性交的感染率为0.08%至0.30%（不包括 包括商业性工作者）。这与肛交的合并风险估计相反， 1.7%至少比阴道性交的风险估计高5-6倍。这些数据表明，HIV-1 在阴道性交过程中传播面临着独特的阴道防御，防止传播和/或早期步骤 HIV-1感染。我们已经鉴定了阴道液外泌体（VFE），并表明VFE可以显著地 减少HIV-1的体外传播。我们假设VFE可以构成HIV-1传播的障碍 在异性接触中。为了验证这一假设，我们将追求以下具体目标：（1）分析 VFE，并确定其组成和来源;（3）确定HIV-1生命周期的步骤， 确定VFE如何阻断HIV-1传播。 具体创新点包括：（1）鉴定女性产生的抗HIV-1的防御机制 感染，（2）新发现的VFE的表征，以及（3）确定 VFE抑制HIV-1传播。我们的研究环境使临床和 基础研究人员，这是该项目取得成功的关键。

Sexual contact is a major mode of HIV-1 transmission, with an increasing number of transmissions occurring via heterosexual contact from males to females. Consequently, about 16 million women worldwide are infected with HIV-1. Heterosexual transmission includes both anal and vaginal sex; the estimated risk of infection from vaginal sex with an HIV-1 positive male ranges from 0.08% to 0.30% per sexual act (not including commercial sex workers). This is in contrast with the pooled risk estimate for anal intercourse, which at 1.7% is at least 5–6 times higher than the risk estimate for vaginal sex. These statistics indicate that HIV-1 transmission during vaginal sex faces unique vaginal defenses that prevent the transmission and/or early steps of HIV-1 infection. We have identified vaginal fluid exosomes (VFE) and shown that VFE can significantly reduce HIV-1 transmission in vitro. We hypothesize that VFE can constitute a barrier to HIV-1 transmission during heterosexual contact. To test this hypothesis, we will pursue the following Specific Aims: (1) Analyze VFE and determine their composition and their source; (3) Identify the step(s) of the HIV-1 life cycle that are targeted by VFE; and (3) Determine how VFE block HIV-1 transmission. Specific points of innovation include (1) identification of female-produced defenses against HIV-1 infection, (2) characterization of the newly discovered VFE, and (3) identification of the mechanism by which VFE inhibit HIV-1 transmission. Our research environment enables close collaboration between clinical and basic researchers, which is crucial for the successful outcome of this project.