Identification of differentially expressed proteins in the cervical mucosa of HIV-1-resistant sex workers.
Novel tools are necessary to understand mechanisms of altered susceptibility to HIV-1 infection in women of the Pumwani Sex Worker cohort, Kenya. In this cohort, more than 140 of the 2000 participants have been characterized to be relatively resistant to HIV-1 infection. Given that sexual transmission of HIV-1 occurs through mucosal surfaces such as that in the cervicovaginal environment, our hypothesis is that innate immune factors in the genital tract may play a role in HIV-1 infection resistance. Understanding this mechanism may help develop microbicides and/or vaccines against HIV-1. A quantitative proteomics technique (2D-DIGE: two-dimensional difference in-gel electrophoresis) was used to examine cervical mucosa of HIV-1 resistant women ( n = 10) for biomarkers of HIV-1 resistance. Over 15 proteins were found to be differentially expressed between HIV-1-resistant women and control groups ( n = 29), some which show a greater than 8-fold change. HIV-1-resistant women overexpressed several antiproteases, including those from the serpin B family, and also cystatin A, a known anti-HIV-1 factor. Immunoblotting for a selection of the identified proteins confirmed the DIGE volume differences. Validation of these results on a larger sample of individuals will provide further evidence these biomarkers are associated with HIV-1 resistance and could help aid in the development of effective microbicides against HIV-1.
Burgener
Adam
A
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2. burgener@cc.umanitoba.ca
Boutilier
Julie
J
Wachihi
Charles
C
Kimani
Joshua
J
Carpenter
Michael
M
Westmacott
Garrett
G
Cheng
Keding
K
Ball
Terry B
TB
Plummer
Francis
F
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002584:Cervix Uteri / Q000033:anatomy & histology / Q000821:virology; D005260:Female; D015488:HIV Antigens / Q000032:analysis*; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission; D015497:HIV-1 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007630:Kenya; D008875:Middle Aged; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000821:virology*; D011477:Sex Work
D015415:Biomarkers; D015488:HIV Antigens