Transmission of human immunodeficiency virus from monocytes to epithelia

Abstract

Physical contact between latent HIV-infected monocytes and epithelial cells appears to trigger rapid assembly and release of HIV into the enclosed space between donor and acceptor cells. During this process, monocytes form microvilli that intimately associate with epithelial membrane. HIVs sequestered in these sites are then internalized in the epithelial cells within phagocytic endosomes. Morphological evidence suggests that parts of virions fuse with the endosomal membrane and escape into the cytoplasm of the epithelium before endosome-lysosome fusion. In addition, virions in the lysosomal compartment are not necessarily degraded and may cause dissolution of phagolysosome membrane before HIV is damaged. This is reflected in the observation of free coated virions in the epithelial cytoplasm. Apart from the phagocytic mode of HIV entry, two other less common routes of HIV penetration were observed. One resembles direct HIV fusion with host membrane, which is similar to the entry mode of virus into CD4 lymphocytes. The second mode of entry resembles receptor-mediated endocytosis characterized by small pits and endosomes. Cell contact-mediated viral shedding and the diversity of HIV entry mechanisms are described for an in vitro model.