HIV Transcytosis via Adult and Fetal Oral Epithelial Cells

Objectives: Oral transmission is a potentially important route of HIV infection. The oropharyngeal epithelium of the fetus/neonate may serve as an efficient portal of entry for perinatal/postnatal mother-to-child transmission (MTCT) of HIV, yet oral HIV transmission among adults is rare. The reasons for this difference are not well understood. Our goal was to investigate the mechanisms of transmission of HIV via adult and fetal oral epithelium.

Methods: HIV transcytosis was investigated using adult and fetal oropharyngeal tissue explants, and polarized epithelial cells. HIV transcytosis was evaluated by confocal microscopy, ELISA and reverse transcriptase assays.

Results: Addition of HIV-1 to the mucosal surface of adult oral epithelium led to penetration of virions into only the upper part of the stratified epithelium (2-5 layers), and virus never reached the spinosum/basal layers or lamina propria. In contrast, incubation of fetal oropharyngeal epithelium with HIV led to transmission of virions across epithelium and penetration into the lamina propria. Analysis of adult and fetal polarized oral epithelial cells showed that HIV transcytosis occurred through both adult and fetal epithelial cells. However, virions that emerged after transcytosis of adult epithelial cells were not infectious, whereas those that passed through fetal epithelial cells were highly infectious. Expression of anti-HIV innate proteins was substantially higher in adult epithelial cells than in fetal cells, suggesting their potential role in viral inactivation.

Conclusions: Our data show that HIV can traverse both adult and fetal oral epithelial cells by transcytosis. In adults, the virions do not pass through stratified epithelium and are rendered noninfectious, consistent with the low rate of oral HIV transmission in adults. Conversely, HIV traverses the fetal epithelium to the lamina propria and remains highly infectious, potentially contributing to HIV MTCT. This project was supported by NIH grants R01 DE14894 and R21 DE016009 (to S.T).