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AIDS (London, England) · 2015

Mx2 expression is associated with reduced susceptibility to HIV infection in highly exposed HIV seronegative Kenyan sex workers.

СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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

Аннотация

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.

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