Mx2 expression is associated with reduced susceptibility to HIV infection in highly exposed HIV seronegative Kenyan sex workers. (2nd January 2015)

• Record Type: Journal Article
• Authors: Stein, Derek R.; Shaw, Souradet Y.; McKinnon, Lyle R.; Abou, Max; McCorrister, Stuart J.; Westmacott, Garrett R.; Fowke, Keith R.; Plummer, Francis A.; Ball, T. Blake
• Is Part Of: AIDS. Volume 29:Number 1(2015)
• Publication Date: 2015-01-02
• Subjects: Depo-Provera -- DMPA -- HIV -- highly exposed HIV-seronegative -- highly exposed HIV seronegative -- Mx2; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000000490
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Introduction: Recent studies have identified Mx2 as a novel HIV-1 innate restriction factor that inhibits proviral integration. A pilot proteomic study of immune cells from highly exposed HIV-seronegative (HESN) individuals enrolled in the Pumwani sex worker cohort identified Mx1 as potential correlate of HIV protection. A detailed population level analysis of Mx1 and Mx2 expression and their role in reduced susceptibility to HIV infection in HESN women was conducted. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from 102 HESN women and 100 high-risk negative controls enrolled in a Nairobi-based sex worker cohort. Whole-cell lysates were prepared and analyzed for Mx1 and Mx2 expression by commercial ELISA. Bivariate and multiple linear regression analyses were conducted to account for confounding epidemiological factors. Results: Mx2, but not Mx1, was found to be significantly overexpressed in HESN women compared with high-risk negative controls ( P = 0.027). After multiple linear regression analysis, accounting for age, menopause, pregnancy, Depo-Provera use, recent infections and medication usage, Mx2 expression remained significantly overexpressed in the PBMC of HESN women ( P = 0.05). Additionally, an interaction model analysis indicated that HESN women who use Depo-Provera have 2.6-fold higher levels of Mx2 than any other group ( P < 0.001). No associations with Mx1 expression were observed. Conclusion: This is the first epidemiological report of Mx2 and its association with altered susceptibility to HIV infection in HESN women. Additionally, we show that HESN women who use Depo-Provera have the highest levels of Mx2 expression, highlighting a possible mechanism for hormonal modulation of HIV susceptibility. Abstract : Supplemental Digital Content is available in the text