Mechanisms of HIV/SIV Mucosal Transmission

Abstract

The Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), organized a Workshop on HIV/SIV Pathogenesis and Mucosal Transmission on March 14-17, 1994, attended by over 300 participants. The purpose of the workshop was to foster research in the areas of HIV pathogenesis, mucosal transmission, and host factors modulating HIV infection and disease. This article summarizes workshop presentations that focused on mechanisms of HIV or SIV mucosal transmission. The following are highlights from the workshop. The epidemiological data indicating a low probability of infection from a single sexual exposure are consistent with observations that infectious cell-free or cell-associated HIV could be isolated from only 10-57% of semen samples, and that high levels of SIV are required for infection by a mucosal route. Several lines of circumstantial evidence suggest that an important property of a transmitted HIV or SIV is the ability to infect macrophages. A potential mechanism for cell-associated mucosal transmission is provided by the observations that CD4-negative epithelial cells in culture are efficiently infected by direct contact with HIV-infected T cells, and that HIV-infected epithelial cells are observed in vivo. Cell-free HIV virions contain partial reverse transcripts of viral RNA into DNA, and conditions that promote DNA reverse transcripts, such as incubation in seminal fluid, increase viral infectivity. Finally, evidence is accumulating that transient or abortive infection with short-term recovery of infectious virus in blood can occur in the absence of seroconversion.

Mucosal and Plasma IgA from HIV-1-Exposed Uninfected Individuals Inhibit HIV-1 Transcytosis Across Human Epithelial Cells

“…This study used an experimental system that mimicked natural HIV-1 infection, in which the first steps of infection involve contact between secretions containing HIV-infected cells or cell-free virus and the mucosal luminal surface (14,30). The mucosal surfaces have a covering of either pluristratified epithelial cells (in the vagina, exocervix, prepuce, and anus) or a simple epithelial monolayer (in the rectum, endocervix, and intestine).…”

Tonsil Epithelial Factors May Influence Oropharyngeal Human Immunodeficiency Virus Transmission

“…The predominant mode of transmission for human immunodeficiency virus (HIV) is through the mucosal route, 1,2 particularly genital and gastrointestinal tract mucosae. To establish infection, HIV must cross the epithelial barrier of the recipient, associate with dendritic cells to infect resident lymphocytes and macrophages, and then spread systemically.…”

Secretory IgA Specific for a Conserved Epitope on gp41 Envelope Glycoprotein Inhibits Epithelial Transcytosis of HIV-1

“…HIV-1 transmission occurs through exposure of mucosal surfaces to HIV-1-infected fluids, such as semen, colostrum, breast milk, and cervicovaginal fluid (2,3). Mucosal Abs in seropositive subjects consistently contain S-IgA specific for HIV-1 envelope glycoproteins (4).…”

“…Two molecules are required for the transcytosis of HIV-1 across CD4-negative epithelial cells (10): the HIV-1 surface envelope glycoprotein subunit gp120 and glycosphingolipid galactosyl ceramide (Gal Cer), 3 which is thought to act as gp120 epithelial cell receptor (14,15). Gal Cer is markedly enriched at the apical surface of epithelial cells (16) and participates in the establishment of microdomains referred to as rafts, which act as platforms for endocytosis (17,18) and transcytosis (19,20).…”