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J Proteome Res DOI:10.1021/pr200596r

Comprehensive proteomic study identifies serpin and cystatin antiproteases as novel correlates of HIV-1 resistance in the cervicovaginal mucosa of female sex workers.

Publication TypeJournal Article
Year of Publication2011
AuthorsBurgener, A, Rahman, S, Ahmad, R, Lajoie, J, Ramdahin, S, Mesa, C, Brunet, S, Wachihi, C, Kimani, J, Fowke, K, Carr, S, Plummer, F, Ball, TB
JournalJ Proteome Res
Volume10
Issue11
Pages5139-49
Date Published2011 Nov 04
ISSN1535-3907
KeywordsAdult, alpha 1-Antitrypsin, alpha-Macroglobulins, Cervix Uteri, Cystatin B, Disease Resistance, Female, Genitalia, Female, HIV Infections, HIV-1, Humans, Middle Aged, Mucous Membrane, Phenotype, Proteomics, Serpins, Sex Workers, Vagina
Abstract

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 =

URLhttp://dx.doi.org/10.1021/pr200596r
DOI10.1021/pr200596r
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/21973077?dopt=Abstract

Alternate JournalJ. Proteome Res.
PubMed ID21973077
Grant List / / Canadian Institutes of Health Research / Canada