Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells
Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells
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DOI：
10.1128/jvi.74.13.6087-6095.2000
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发表时间：
2000-07-01
影响因子：
5.4
通讯作者：
Miller, CJ
中科院分区：
文献类型：
--
作者：
Hu, JJ;Gardner, MB;Miller, CJ
尽管最近对粘膜人类免疫缺陷病毒（HIV）传播的见解，灵长类慢病毒穿过粘膜表面的复层鳞状上皮的途径仍然不确定。为了确定树突状细胞（DC）是否被灵长类慢病毒用于穿越生殖道的上皮屏障，恒河猴阴道内暴露于无细胞猿猴免疫缺陷病毒SIVmac 251。我们检查了福尔马林固定的组织和HLA-DR+富集的细胞悬液，以确定在感染的前24小时内生殖道和引流淋巴结中含有SN RNA的细胞。使用SIV特异性荧光原位杂交结合免疫荧光抗体标记的谱系特异性细胞标志物，大量的SIV RNA（+）DC记录在阴道接种后18小时从阴道上皮细胞悬液。此外，我们确定了SIV接种物必须保持与生殖器粘膜接触以使病毒从阴道腔进入粘膜的最短时间。我们现在表明，SIV在阴道内暴露60分钟内进入阴道粘膜，主要感染上皮内DC，并且SIV感染的细胞在阴道内SIV暴露18小时内位于引流淋巴结中。灵长类慢病毒穿透粘膜表面，感染DC，并传播到引流淋巴结的速度对HIV疫苗的开发提出了严峻的挑战。
Despite recent insights into mucosal human immunodeficiency virus (HIV) transmission, the route used by primate lentiviruses to traverse the stratified squamous epithelium of mucosal surfaces remains undefined. To determine if dendritic cells (DC) are used by primate lentiviruses to traverse the epithelial barrier of the genital tract, rhesus macaques were intravaginally exposed to cell-free simian immunodeficiency virus SIVmac251. We examined formalin-fixed tissues and HLA-DR+-enriched cell suspensions to identify the cells containing SN RNA in the genital tract and draining lymph nodes within the first 24 h of infection. Using SIV-specific fluorescent in situ hybridization combined with immunofluorescent antibody labeling of lineage-specific cell markers, numerous SIV RNA(+) DC were documented in cell suspensions from the vaginal epithelium 18 h after vaginal inoculation. In addition, we determined the minimum time that the SIV inoculum must remain in contact with the genital mucosa for the virus to move from the vaginal lumen into the mucosa, We now show that SIV enters the vaginal mucosa within 60 min of intravaginal exposure, infecting primarily intraepithelial DC and that SIV-infected cells are located in draining lymph nodes within 18 h of intravaginal SIV exposure. The speed with which primate lentiviruses penetrate mucosal surfaces, infect DC, and disseminate to draining Lymph nodes poses a serious challenge to HIV vaccine development.