Derek R Stein1, Souradet Y Shaw, Lyle R McKinnon, Max Abou, Stuart J McCorrister, Garrett R Westmacott, Keith R Fowke, Francis A Plummer, T Blake Ball. 1. aDepartments of Medical Microbiology bCommunity Health Sciences cImmunology University of Manitoba, Winnipeg, Manitoba, Canada dCenter for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R. Mandela School of Medicine, University of KwaZulu-Nata, Durban, South Africa eNational HIV and Retrovirology Laboratories, JC Wilt Infectious Disease Research Centre fMass Spectrometry and Proteomics Core Facility, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
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.
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.
Authors: Wbeimar Aguilar-Jimenez; Irma Saulle; Daria Trabattoni; Francesca Vichi; Sergio Lo Caputo; Francesco Mazzotta; Maria T Rugeles; Mario Clerici; Mara Biasin Journal: Front Immunol Date: 2017-02-13 Impact factor: 7.561
Authors: María Julia Ruiz; Jimena Salido; Lorena Abusamra; Yanina Ghiglione; Cintia Cevallos; Gabriel Damilano; Ana María Rodriguez; César Trifone; Natalia Laufer; Luis D Giavedoni; Omar Sued; Horacio Salomón; María Magdalena Gherardi; Gabriela Turk Journal: EBioMedicine Date: 2017-11-03 Impact factor: 8.143