HIV binding, penetration, and primary infection in human cervicovaginal tissue

Abstract

We have developed human cervicovaginal organ culture systems to examine the initiating events in HIV transmission after exposure to various sources of HIV infectivity, including semen. Newly infected cells were detected in the cervical submucosa 3-4 days after exposure to a primary HIV isolate. At earlier times, extensive and stable binding occurred when cervical surfaces were exposed to virions or seminal cells. Cervical mucus provided some protection for the endocervical surface, by physically trapping virions and seminal cells. Confocal microscopy combined with 3D surface reconstruction revealed that virions could both bind to the external surface of the cervical epithelium and actually penetrate beneath the epithelial surface. In quantitative assays, pretreatment with a blocking antibody directed against ␤1 integrin reduced HIV virion binding. Collectively, these results highlight a continuum of complex interactions that occurs when natural sources of HIV infectivity are deposited onto mucosal surfaces in the female reproductive tract.confocal microscopy ͉ female reproductive tissue ͉ HIV transmission ͉ organ culture ͉ tissue surface reconstruction

Comprehensive Proteomic Analysis of Human Cervical−Vaginal Fluid

“…13 Previous studies have also identified a role for CVF in the trapping of HIV virions, thus, preventing infection. 14,15 Recent studies have detected a correlation between several immuneresponse molecules in CVF and the incidence of subclinical premature rupture of membranes (PROM), which leads to preterm birth. 16,17 During pregnancy, CVF could contain amniotic fluid (AF) derived from the uterus, due to either the disruption or parallel secretions of the chorionic-decidual interface.…”

Differential Transmission of HIV Traversing Fetal Oral/Intestinal Epithelia and Adult Oral Epithelia

“…Explants were placed with the mucosal side facing up in the top chamber of Millicell filter inserts (Millipore) (diameter, 12 mm; pore size, 0.4 m). The lateral edges of the explants were sealed with 3% agarose, as described previously (11,30,31). The orientation of the explants was monitored using a stereomicroscope (Stereomaster; Fisher Scientific).…”

Humanes Immunschwächevirus (HIV)

“…[63], in den regionalen Lymphknoten innerhalb von etwa 5 bis 6 Tagen und im ganzen Körper verteilt, einschließlich des Nervensystems, innerhalb von etwa 10 bis 14 Tagen, wobei ein Unterschied in der Geschwindigkeit der Verbreitung besteht, wenn primär Zellen der Tonsillen oder der rektalen Mukosa infiziert wurden [64].…”