title: Mx2 expression is associated with reduced susceptibility to HIV infection in highly exposed HIV seronegative Kenyan sex workers.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Derek R
authors.initials: DR
authors.lastname: Stein
authors.forename: Souradet Y
authors.initials: SY
authors.lastname: Shaw
authors.forename: Lyle R
authors.initials: LR
authors.lastname: McKinnon
authors.forename: Max
authors.initials: M
authors.lastname: Abou
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: McCorrister
authors.forename: Garrett R
authors.initials: GR
authors.lastname: Westmacott
authors.forename: Keith R
authors.initials: KR
authors.lastname: Fowke
authors.forename: Francis A
authors.initials: FA
authors.lastname: Plummer
authors.forename: T Blake
authors.initials: TB
authors.lastname: Ball
mesh_terms: D000328:Adult; D004198:Disease Susceptibility / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000453:epidemiology; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007113:Immunity, Innate; D007630:Kenya / Q000453:epidemiology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D064547:Myxovirus Resistance Proteins / Q000276:immunology*; D040901:Proteomics; D060386:Sex Workers
chemical_list: C579071:MX1 protein, human; C579068:MX2 protein, human; D064547:Myxovirus Resistance Proteins; D017258:Medroxyprogesterone Acetate