Comprehensive Proteomic Study Identifies Serpin and Cystatin Antiproteases as Novel Correlates of HIV-1 Resistance in the Cervicovaginal Mucosa of Female Sex Workers

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...

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Bibliographic Details
Published in:Journal of proteome research 2011-11, Vol.10 (11), p.5139-5149
Main Authors: Burgener, A, Rahman, S, Ahmad, R, Lajoie, J, Ramdahin, S, Mesa, C, Brunet, S, Wachihi, C, Kimani, J, Fowke, K, Carr, S, Plummer, F, Ball, T. B
Format: Article
Language:English
Subjects:
Adult
alpha 1-Antitrypsin - genetics
alpha 1-Antitrypsin - metabolism
alpha-Macroglobulins - genetics
alpha-Macroglobulins - metabolism
Cervix Uteri - metabolism
Cystatin B - genetics
Cystatin B - metabolism
Disease Resistance - genetics
Female
Genitalia, Female - metabolism
HIV Infections - genetics
HIV Infections - metabolism
HIV-1
Humans
Middle Aged
Mucous Membrane - metabolism
Phenotype
Proteomics
Serpins - genetics
Serpins - metabolism
Sex Workers
Vagina - metabolism
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Summary: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 =
ISSN:1535-3893
1535-3907
DOI:10.1021/pr200596r