458 Human Urogenital Epithelial Cells Capture Cell-free HIV-1 and Transmit the Virus to CD4+ Cells-Implications to Mechanisms of Sexual Transmission Z. Wu*1, Z. Chen2, D. Phillips3 1Univ of Pennsylvania, Philadelphia; 2Aaron Diamond AIDS Res Ctr, New York, NY; and 3Pop Council, New York, NY
Background: Sexual transmission of HIV-1 has become the dominant route of the epidemic, especially in parts of the world where preventative resources are limited, therapeutics are inaccessible to the majority of the population, and genital-related illnesses are prevalent. However, despite profound understanding of the life cycle of the virus, little is known on how the virus breaks through the genital mucosal barrier, disseminates to peripheral lymphoid tissues, and establishes systemic infection.
Methods: We investigated whether HIV-1 infected genital epithelial cells and how, subsequently, the virus disseminated to CD4+ cells by developing a genital epithelial cell-based co-culture system to understand the sexual transmission of the virus.
Results: We found that 1) HIV does not productively infect genital epithelial cells, instead the virus was sequestered by the cells via a specific receptor, similar to DC-SIGN on dendritic cells; 2) the sequestered virus remains infectious for a prolonged period; 3) the epithelial cell-attached virus could be efficiently transmitted to CD4+ cells through cell-cell contact; and 4) M-tropic isolates appeared to be transmitted significantly more efficiently than T-tropic isolates.
Conclusion: HIV-1 does not productively infect genital epithelial cells; instead the virus becomes sequestered by the cells and remains infectious for a prolonged period. The sequestered virus can efficiently infect CD4+ cells via cell-cell contact and M-tropic isolates are more readily transmitted to these CD4+ cells. We will discuss the mechanism of sexual transmission of HIV and selective viral transmission, its significance and implication for vaccine development, and other preventative measures.
