The female genital epithelium is assumed to play a protective role against invading pathogens, such as HIV. Although male-to-female sexual transmission of HIV is inefficient in the absence of facilitating factors, it remains the most common mode of HIV transmission . To understand the role of the female genital epithelial cells in sexual transmission, we studied the interaction between the ectocervical (Ect1) and endocervical (End1) cell lines and HIV. Using fluorescent protein-expressing recombinant HIV, we observed that both ectocervical and endocervical epithelial cells were capable of internalizing cell-free HIV, and to a much lesser extent, cell-associated HIV. Cervical epithelial cell internalization of cell-free HIV (carrying primary transmitted/founder envelope genes cloned within full-length molecular clones), lead to a productive infection. This infection of Ect1 and End1 cells occurred in a CD4-independent manner and was increased ~2-5 fold when inoculation occurred in the presence of Semen-derived Enhancer of Virus (SEVI), an endogenous enhancement factor found in semen. Once infected, the Ect1 and End1 cells were capable of infecting target CD4 T cells in co-culture in a cell-associated manner. The infection of CD4 T cells occurred only when de novo HIV was produced within the epithelial cells and was inhibited by the CD4-blocking antibody (Leu3A) and the co-receptor antagonist (TAK779). These findings suggest that cervical epithelial cells may participate in establishing an HIV infection and should be targeted when designing prevention strategies to protect against HIV sexual transmission.
|Advisor:||Klotman, Mary E., Chen, Benjamin K.|
|Commitee:||Fernandez-Sesma, Ana, Hioe, Catarina, Simon, Viviana, Tortorella, Domenico|
|School:||Icahn School of Medicine at Mount Sinai|
|School Location:||United States -- New York|
|Source:||DAI-B 74/06(E), Dissertation Abstracts International|
|Subjects:||Cellular biology, Microbiology, Virology, Immunology|
|Keywords:||CD4+ T cells, Cervical epithelial cells, Ectocervical, Endocervical, Hiv infection|
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