Human immunodeficiency virus interaction with oral and genital mucosal epithelia may lead to epithelial-mesenchymal transition and sequestration of virions in the endosomal compartments.

Oral and genital mucosal epithelia are multistratified epithelial barriers with well-developed tight and adherens junctions. These barriers serve as the first line of defense against many pathogens, including human immunodeficiency virus (HIV). HIV interaction with the surface of mucosal epithelial cells, however, may activate transforming growth factor-beta (TGF-β) and mitogen-activated protein kinase signaling pathways. When activated, these pathways may lead to the disruption of epithelial junctions and epithelial-mesenchymal transition (EMT). HIV-induced impairment of the mucosal barrier may facilitate the spread of pathogenic viral, bacterial, fungal, and other infectious agents. HIV-induced EMT promotes highly motile/migratory cells. In oral and genital mucosa, if EMT occurs within a human papillomavirus (HPV)-infected premalignant or malignant cell environment, the HPV-associated neoplastic process could be accelerated by promoting viral invasion of malignant cells. HIV also internalizes into oral and genital mucosal epithelial cells. The majority (90%) of internalized virions do not cross the epithelium, but are retained in endosomal compartments for several days. These sequestered virions are infectious. Upon interaction with activated peripheral blood mononuclear cells and CD4+ T lymphocytes, epithelial cells containing the virus can be transferred. The induction of HIV-1 release and the cell-to-cell spread of virus from epithelial cells to lymphocytes is mediated by interaction of lymphocyte receptor function-associated antigen-1 with the epithelial cell receptor intercellular adhesion molecule-1. Thus, mucosal epithelial cells may serve as a transient reservoir for HIV, which could play a critical role in viral transmission.