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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Comprehensive proteomic study identifies serpin and cystatin antiproteases as novel correlates of HIV-1 resistance in the cervicovaginal mucosa of female Sex workers
Journal of Proteome Research, Volume 10, No. 11, Year 2011
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Description
Not all individuals exposed to HIV-1 become infected, and evidence from HIV-1 highly exposed seronegative women (HIV-1-resistant) suggests that mucosal factors in the female genital tract, the first site of contact for the virus, are playing a role. To better understand factors mediating protection from HIV-1, we performed a large clinical study using the tools of systems biology to fully characterize the cervicovaginal mucosa proteome in HIV-1-resistant women. Cervicovaginal lavage fluid was collected from 293 HIV-1-resistant, uninfected, and infected sex workers and analyzed by 2D-LC LTQ-FT-MS. Of the more than 360 unique proteins identified, 41 were differentially abundant (>3-fold cutoff) in HIV-1-resistant women. The majority of over-abundant proteins were antiproteases (>40%), some with described anti-inflammatory and anti-HIV-1 activity. Quantification of specific anti-HIV-1 antiproteases Serpin A1, Serpin A3, and Cystatin B and an epithelial antiprotease A2ML1 found them to be significantly over-abundant in HIV-1-resistant women (p = 0.004; p = 0.046; p = 0.0003; and p = 0.04, respectively). Expression levels were not correlated to sexual practices or other epidemiological factors. Mucosal antiprotease levels correlated with pro-inflammatory cytokine concentration (p = <0.0001), but independently of pro-inflammatory cytokine levels in HIV-1-resistant women including TNF-alpha, IL-1 alpha, IL-1 beta, IL-6, and IL-8. This comprehensive systems biology approach identifies mucosal serpins and cystatins as novel correlates of HIV-1-resistance. This represents the first study characterizing these factors in the female genital tract. © 2011 American Chemical Society.
Authors & Co-Authors
Burgener, Adam D.
Canada, Winnipeg
University of Manitoba
Rahman, S.
Canada, Winnipeg
University of Manitoba
Ahmad, Rushdy
United States, Cambridge
Massachusetts Institute of Technology
Lajoie, Julie
Canada, Winnipeg
University of Manitoba
Ramdahin, Sue G.
Canada, Winnipeg
University of Manitoba
Mesa, Christine
Canada, Ottawa
Public Health Agency of Canada
Brunet, S.
Canada, Ottawa
Public Health Agency of Canada
Wachihi, Charles
Kenya, Nairobi
University of Nairobi
Kimani, Joshua
Canada, Winnipeg
University of Manitoba
Kenya, Nairobi
University of Nairobi
Fowke, Keith Raymond
Canada, Winnipeg
University of Manitoba
Kenya, Nairobi
University of Nairobi
Carr, Steven Alfred
United States, Cambridge
Massachusetts Institute of Technology
Plummer, Francis Allan
Canada, Winnipeg
University of Manitoba
Canada, Ottawa
Public Health Agency of Canada
Ball, Terry Blake
Canada, Winnipeg
University of Manitoba
Kenya, Nairobi
University of Nairobi
Canada, Ottawa
Public Health Agency of Canada
Statistics
Citations: 72
Authors: 13
Affiliations: 4
Identifiers
Doi:
10.1021/pr200596r
ISSN:
15353893
e-ISSN:
15353907
Research Areas
Infectious Diseases
Sexual And Reproductive Health
Participants Gender
Female