Bacterial vaginosis (BV), a common female reproductive tract (FRT) condition characterized by an overgrowth of anaerobic species concurrent with the disappearance of commensal Lactobacilli species, is associated with a 60% increased risk of HIV-1 transmission. However, the role of the FRT epithelia in bacterial vaginosis-associated bacteria (BVAB)-augmented HIV- 1 transmission is unclear. To evaluate the increased risk of HIV-1 acquisition, we treated FRT epithelia with Atopobium vaginae, a prevalent BVAB, to determine the nature of the host response to BVAB exposure. Treatment of endocervical cells with A. vaginae resulted in a 1500-fold increase in the expression of the antimicrobial peptide hBD-2, an inflammatory cytokine response, and delocalization of the tight junction protein ZO-1 from cell borders. Conditioned media (CM) from the coculture of FRT epithelia and A. vaginae also generated an inflammatory immune response and lowered the transepithelial electrical resistance in polarized endocervical monolayers. Changes in HIV-1 infection were measured in TZM-bl reporter cells, which contain a luciferase gene under the control of an HIV-1 long terminal repeat (LTR) region that is activated by the binding of Tat, an HIV-1 protein that drives viral replication. NFκB is a major host-derived transcription factor that regulates the expression of many genes involved in inflammation and the innate immune response. Interestingly, NFκB has been reported to bind Tat-activated response elements within the LTR of HIV-1, driving viral transcription. TZM-bl cells were treated with CM in the absence of HIV-1, which resulted in increased luciferase production that could be suppressed by the NFκB inhibitor TPCA-1. These data suggest that epithelially derived products from the coculture of FRT cells and A. vaginae enhance HIV-1 infection by causing cervical barrier dysfunction and increasing HIV replication efficiency through NFκB.
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Cole, Alexander M.
Bachelor of Science (B.S.)
College of Medicine
Dissertations, Academic -- Medicine; Medicine -- Dissertations, Academic
Length of Campus-only Access
Honors in the Major Thesis
Nguyen, April, "The Effect of Bacterial Vaginosis Associated Bacteria on Epithelial Factors Mediating HIV Transmission" (2015). HIM 1990-2015. 1847.