Dataset Information

High level of soluble HLA-G in the female genital tract of Beninese commercial sex workers is associated with HIV-1 infection.

ABSTRACT:

Background

Most HIV infections are transmitted across mucosal epithelium. Understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, are of fundamental importance. HLA-G is a powerful modulator of the immune response. The aim of this study was to investigate whether soluble HLA-G (sHLA-G) expression in the female genital tract is associated with HIV-1 infection.

Methods and findings

Genital levels of sHLA-G were determined in 52 HIV-1-uninfected and 44 antiretroviral naïve HIV-1-infected female commercial sex workers (CSWs), as well as 71 HIV-1-uninfected non-CSW women at low risk of exposure, recruited in Cotonou, Benin. HIV-1-infected CSWs had higher genital levels of sHLA-G compared with those in both the HIV-1-uninfected CSW (P?=?0.009) and non-CSW groups (P?=?0.0006). The presence of bacterial vaginosis (P?=?0.008), and HLA-G*01:01:02 genotype (P?=?0.002) were associated with higher genital levels of sHLA-G in the HIV-1-infected CSWs, whereas the HLA-G*01:04:04 genotype was also associated with higher genital level of sHLA-G in the overall population (P?=?0.038). When adjustment was made for all significant variables, the increased expression of sHLA-G in the genital mucosa remained significantly associated with both HIV-1 infection (P?=?0.02) and bacterial vaginosis (P?=?0.03).

Conclusion

This study demonstrates that high level of sHLA-G in the genital mucosa is independently associated with both HIV-1 infection and bacterial vaginosis.

SUBMITTER: Thibodeau V

PROVIDER: S-EPMC3179477 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

High level of soluble HLA-G in the female genital tract of Beninese commercial sex workers is associated with HIV-1 infection.

Thibodeau Valérie V Lajoie Julie J Labbé Annie-Claude AC Zannou Marcel D MD Fowke Keith R KR Alary Michel M Poudrier Johanne J Roger Michel M

PloS one 20110923 9

<h4>Background</h4>Most HIV infections are transmitted across mucosal epithelium. Understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, are of fundamental importance. HLA-G is a powerful modulator of the immune response. The aim of this study was to investigate whether soluble HLA-G (sHLA-G) expression in the female genital tract is associated with HIV-1 infection.<h4>Metho ...[more]

PMID: 21966450

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Project description:BackgroundAlthough female sex workers (FSWs) report high levels of condom use with commercial sex clients, particularly after targeted HIV preventive interventions have been implemented, condom use is often low with non-commercial partners. There is limited understanding regarding the factors that influence condom use with FSWs' non-commercial partners, and of how programs can be designed to increase condom use with these partners. The main objectives of this study were therefore to describe FSWs' self-reported non-commercial partners, along with interpersonal factors characterizing their non-commercial partnerships, and to examine the factors associated with consistent condom use (CCU) within non-commercial partnerships.MethodsThis study used data collected from cross-sectional questionnaires administered to 988 FSWs in four districts in Karnataka state in 2006-07. We used bivariate and multivariable logistic regression analysis to examine the relationship between CCU (i.e., 'always' compared to 'never', 'sometimes' or 'frequently') with non-commercial partners of FSWs (including the respondents' husband or main cohabiting partner [if not married] and their most recent non-paying partner [who is neither a husband nor the main cohabiting partner, and with whom the FSW had sex within the previous year]) and interpersonal factors describing these partnerships, as well as social and environmental factors. Weighting and survey methods were used to account for the cluster sampling design.ResultsOverall, 511 (51.8%) FSWs reported having a husband or cohabiting partner and 247 (23.7%) reported having a non-paying partner. CCU with these partners was low (22.6% and 40.3% respectively). In multivariable analysis, the odds of CCU with FSWs' husband or cohabiting partner were 1.8-fold higher for FSWs whose partner knew she was a sex worker (adjusted odds ratio [AOR]: 1.84, 95% confidence intervals[CI]: 1.02-3.32) and almost 6-fold higher if the FSW was unmarried (AOR: 5.73, 95%CI: 2.79-11.76]. CCU with FSWs' non-paying partner decreased by 18% for each one-year increase in the duration of the relationship (AOR: 0.82, 95%CI: 0.68-0.97).ConclusionsThis study revealed important patterns and interpersonal determinants of condom use within non-commercial partnerships of FSWs. Integrated structural and community-driven HIV/STI prevention programs that focus on gender and reduce sex work stigma should be investigated to increase condom use in non-commercial partnerships.

Project description:ObjectiveCationic proteins found in cervicovaginal secretions (CVS) are known to contribute to the early antiviral immune response against HIV-infection in vitro. We here aimed to define additional antiviral factors that are over-expressed in CVS from female sex workers at high risk of infection.MethodsCVS were collected from Kenyan HIV-seronegative (n = 34) and HIV-seropositive (n = 12) female sex workers, and were compared with those from HIV-seronegative low-risk women (n = 12). The highly exposed seronegative (HESN) sex workers were further divided into those with less (n = 22) or more (n = 12) than three years of documented sex work. Cationic protein-depleted CVS were assessed for HIV-neutralizing activity by a PBMC-based HIV-neutralizing assay, and then characterized by proteomics.ResultsHIV neutralizing activity was detected in all unprocessed CVS, however only CVS from the female sex worker groups maintained its HIV neutralizing activity after cationic protein-depletion. Differentially abundant proteins were identified in the cationic protein-depleted secretions including 26, 42, and 11 in the HESN>3 yr, HESN<3 yr, and HIV-positive groups, respectively. Gene ontology placed these proteins into functional categories including proteolysis, oxidation-reduction, and epidermal development. The proteins identified in this study include proteins previously associated with the HESN phenotype in other cohorts as well as novel proteins not yet associated with anti-HIV activities.ConclusionWhile cationic proteins appear to contribute to the majority of the intrinsic HIV neutralizing activity in the CVS of low-risk women, a broader range of non-cationic proteins were associated with HIV neutralizing activity in HESN and HIV-positive female sex workers. These results indicate that novel protein factors found in CVS of women with high-risk sexual practices may have inherent antiviral activity, or are involved in other aspects of anti-HIV host defense, and warrant further exploration into their mode of action.

Project description:Highly Exposed-Seronegatives (HESN) individuals do not contract HIV-1 infection despite long-term exposure; few comprehensive studies examining behavior, mucosal tissue, and peripheral immune parameters in sexually-exposed HESN have been completed. To this end, we assessed rate of condomless vaginal sex, the immune activation status (peripheral blood) and gene expression (ectocervical biopsies) in female cohort of high-risk female sex workers [FSW] (n=50) and non-sex worker women [CG] (n=32) in San Juan, Puerto Rico, USA. Of the 50 FSWs examined only 5 had detectable anti-HIV responses by either HIV gag-specific CD8+ T-Cell responses or mucosal anti-HIV envelope IgG/IgA. FSW had a uniform lower CD38 expression on circulating CD4+ or CD8+ T-Cells (both: p<0.0001:Wilcoxon Rank Sum). Cervical tissue from FSWs had greater levels of CD4+ T-Cell (p=0.040), CD123+ plasmacytoid Dendritic Cells (p=0.013) and CD68+ macrophage infiltrates (p=0.038). Cervical gene expression by RNA microarray indicated that FSW had a gene signature characterized by lower expression of genes associated with leukocyte homing and chemotaxis; partial interferon regulated gene signature; and lower gene expression of genes required for HIV infection such as CD4 and NUP153 indicating a lower mucosal immune activation state and reduced susceptibility to HIV-1 infection within mucosal tissue. Notably, Interferon (IFN)-ε expression was higher in FSW than CG women, as detected by RNA (microarray) and protein (IHC) expression in cervical epithelium. The observed levels of IFNε were associated with the reported frequency of unprotected intercourse. Finally, IFNε was induced by treatment of the ECT1 cell line with seminal fluid, suggesting that semen exposure may contribute to long-term protection. Decreased levels of immune activation and gene expression required for HIV infection along with semen-induced epithelial Interferon ε production within the reproductive tract of FSWs highlight distinct host intrinsic resistance mechanisms that may contribute to long-term HIV seronegative status in spite of high-risk condomless sex.

Dataset Information

High level of soluble HLA-G in the female genital tract of Beninese commercial sex workers is associated with HIV-1 infection.

Background

Methods and findings

Conclusion

Publications

High level of soluble HLA-G in the female genital tract of Beninese commercial sex workers is associated with HIV-1 infection.

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