title: HIV-1-negative female sex workers sustain high cervical IFNɛ, low immune activation, and low expression of HIV-1-required host genes.
abstract: 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.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Abdulhaqq
authors.affiliation: Maternal-Infant Study Center (CEMI), University of Puerto Rico, San Juan, Puerto Rico.
authors.forename: C
authors.initials: C
authors.lastname: Zorrilla
authors.affiliation: School of Biological Sciences and Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska, USA.
authors.forename: G
authors.initials: G
authors.lastname: Kang
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: X
authors.initials: X
authors.lastname: Yin
authors.affiliation: Maternal-Infant Study Center (CEMI), University of Puerto Rico, San Juan, Puerto Rico.
authors.forename: V
authors.initials: V
authors.lastname: Tamayo
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Seaton
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: J
authors.initials: J
authors.lastname: Joseph
authors.affiliation: Maternal-Infant Study Center (CEMI), University of Puerto Rico, San Juan, Puerto Rico.
authors.forename: S
authors.initials: S
authors.lastname: Garced
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Linn
authors.affiliation: Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, Massachusetts, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Foulkes
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: L
authors.initials: L
authors.lastname: Azzoni
authors.affiliation: University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
authors.forename: M
authors.initials: M
authors.lastname: VerMilyea
authors.affiliation: University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
authors.forename: C
authors.initials: C
authors.lastname: Coutifaris
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Kossenkov
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: L
authors.initials: L
authors.lastname: Showe
authors.affiliation: Department of Microbiology, UPR Medical School, San Juan, Puerto Rico.
authors.forename: E N
authors.initials: EN
authors.lastname: Kraiselburd
authors.affiliation: School of Biological Sciences and Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Montaner
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002584:Cervix Uteri / Q000473:pathology; D004198:Disease Susceptibility; D005260:Female; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D007370:Interferon Type I / Q000378:metabolism; D007372:Interferons / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D009092:Mucous Membrane / Q000276:immunology* / Q000821:virology; D012661:Semen / Q000276:immunology; D060386:Sex Workers; D012725:Sexual Behavior; D016662:Virus Integration / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: C524005:IFNE protein, human; D007370:Interferon Type I; D007372:Interferons