Human Immunodeficiency Virus Type 1 Is Trapped by Acidic but Not by Neutralized Human Cervicovaginal Mucus
Human Immunodeficiency Virus Type 1 Is Trapped by Acidic but Not by Neutralized Human Cervicovaginal Mucus
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DOI：
10.1128/jvi.01899-08
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发表时间：
2009-11-01
影响因子：
5.4
通讯作者：
Hanes, Justin
中科院分区：
文献类型：
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作者：
Lai, Samuel K.;Hida, Kaoru;Hanes, Justin
为了可靠地感染人类免疫缺陷病毒（HIV）的灵长类动物模型，阴道必须比静脉注射多10，000倍的病毒。然而，阴道机制，有助于防止艾滋病毒知之甚少。在这里，我们报告说，人类宫颈阴道粘液（CVM），从捐赠者与正常的乳酸杆菌为主的阴道植物群，有效地捕获艾滋病毒，使其扩散速度比在水中慢1,000倍以上。乳酸杆菌通过连续产生乳酸将CVM酸化至pH接近4。在这种酸性pH值下，我们发现乳酸而不是HCl消除了HIV表面的负电荷，而没有溶解病毒膜。相比之下，当精液暂时中和阴道时，在中和至pH 6至7的CVM中，HIV保持其天然表面电荷，扩散速度仅比在水中慢15倍。因此，在性交过程中保持高乳酸含量和酸性的方法可能有助于阴道和阴茎的保护，通过在HIV到达靶细胞之前捕获HIV。我们的研究结果表明，CVM可能在降低艾滋病毒性传播率方面发挥重要但目前未得到重视的作用。
To reliably infect a primate model for human immunodeficiency virus (HIV), similar to 10,000-fold more virus must be delivered vaginally than intravenously. However, the vaginal mechanisms that help protect against HIV are poorly understood. Here, we report that human cervicovaginal mucus (CVM), obtained from donors with normal lactobacillus-dominated vaginal flora, efficiently traps HIV, causing it to diffuse more than 1,000-fold more slowly than it does in water. Lactobacilli acidify CVM to pH similar to 4 by continuously producing lactic acid. At this acidic pH, we found that lactic acid, but not HCl, abolished the negative surface charge on HIV without lysing the virus membrane. In contrast, in CVM neutralized to pH 6 to 7, as occurs when semen temporarily neutralizes the vagina, HIV maintained its native surface charge and diffused only 15-fold more slowly than it would in water. Thus, methods that can maintain both a high lactic acid content and acidity for CVM during coitus may contribute to both vaginal and penile protection by trapping HIV before it can reach target cells. Our results reveal that CVM likely plays an important but currently unappreciated role in decreasing the rate of HIV sexual transmission.