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Mucosal Immunol. 2016 Jul;9(4):1027-38. doi: 10.1038/mi.2015.116. Epub 2015 Nov 11.

HIV-1-negative female sex workers sustain high cervical IFNɛ, low immune activation, and low expression of HIV-1-required host genes.

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The Wistar Institute, Philadelphia, Pennsylvania, USA.
Maternal-Infant Study Center (CEMI), University of Puerto Rico, San Juan, Puerto Rico.
School of Biological Sciences and Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska, USA.
Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, Massachusetts, USA.
University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
Department of Microbiology, UPR Medical School, San Juan, Puerto Rico.


Sex workers practicing in high HIV endemic areas have been extensively targeted to test anti-HIV prophylactic strategies. We hypothesize that in women with high levels of genital exposure to semen changes in cervico-vaginal mucosal and/or systemic immune activation will contribute to a decreased susceptibility to HIV-1 infection. To address this question, we assessed sexual activity and immune activation status (in peripheral blood), as well as cellular infiltrates and gene expression in ectocervical mucosa biopsies in female sex workers (FSWs; n=50), as compared with control women (CG; n=32). FSWs had low-to-absent HIV-1-specific immune responses with significantly lower CD38 expression on circulating CD4(+) or CD8(+) T-cells (both: P<0.001) together with lower cervical gene expression of genes associated with leukocyte homing and chemotaxis. FSWs also had increased levels of interferon-ɛ (IFNɛ) gene and protein expression in the cervical epithelium together with reduced expression of genes associated with HIV-1 integration and replication. A correlative relationship between semen exposure and elevated type-1 IFN expression in FSWs was also established. Overall, our data suggest that long-term condomless sex work can result in multiple changes within the cervico-vaginal compartment that would contribute to sustaining a lower susceptibility for HIV-1 infection in the absence of HIV-specific responses.

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