MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/v01/MSV000078506/primaryOK2000000Proteomicshttps://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=5658e73ee85c4cfab88b698d62dbf66dMassIVE55Not 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.Comprehensive proteomic study identifies serpin and cystatin antiproteases as novel correlates of HIV-1 resistance in the cervicovaginal mucosa of female sex workers.Burgener A A, Rahman S S, Ahmad R R, Lajoie J J, Ramdahin S S, Mesa C C, Brunet S S, Wachihi C C, Kimani J J, Fowke K K, Carr S S, Plummer F F, Ball T B TBCystatin, Mucosa, Cystatins, Prostitutes., Type 2 Cystatins, Muscularis Mucosae, cysteine protease inhibitor activity, Type III, Human immunodeficiency virus 1, Type II Cystatins, Worker Clients, Stefins, Client, Sex Worker Clients, Sex Worker Client, Muscularis, Serpin Protease, Human, Mucosal, Serpin Peptidase, Human Immunodeficiency Virus Type 1, mucosal region, Mucosae, Immunodeficiency Virus Type 1, resistance, Worker Client, Serpin, Cystatin-Related Proteins, Inhibitors, Stefin, serpin, Type III Cystatins, Type I, Lamina Propria, Serpin Protease Inhibitors, Mucosal Tissue, 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Antiprotease, Mucous Membranes, Antiproteases, Peptide Hydrolase Inhibitors, Endopeptidase, Peptide Peptidohydrolase Inhibitor, Type II, Inhibitor, thiol protease inhibitor, Females, Mucosal Tissues293 cell, SPAAT, Viridae, Myeloid Differentiation-Inducing Protein, CDF, Tumor Necrosis Factor Ligand Superfamily Member 2, Granulocyte, LYNAP, Monocyte-derived neutrophil chemotactic factor, IL-1 beta, Conflict Resolution, Myeloid, Ass-1, Type 2 Cystatins, alpha 1, Granulocyte Chemotactic Peptide Interleukin 8, Hepatocyte-Stimulating Factor, fluid, CG17228, 1135/09, 1135/07, B Cell, B Cell Stimulatory Factor 2, Trypsin Inhibitor, Protease Inhibitor, 0451/09, Interferon beta-2, Chemokine, fold, Hybridoma growth factor, HEK 293, Human Embryonic Kidney 293, IL8|NAP1 form III, myd, Monocyte-Derived Neutrophil Chemotactic Factor, 0244/09, Sex, Tissue, DROPROSA, Mbp-1, IL8|NAP1 form IV, Lamina, DIF, 671/2, B Cell Differentiation Factor 2, interleukin-6 receptor ligand, Peptidohydrolase Inhibitor, 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(Ser-IL-8)72, Stefins, Woman, Client, Sex Worker Client, Peptide, l(3)rJ806, Pros, viruses, tnfsf2, Mediating, Interleukin 1alpha, Alpha-1 protease inhibitor, N-terminal fragment, Systems, Protein, Neutrophil Activating Peptide, TFIID, Stefin, IL-8(9-77), Zoophaginae, alpha 1 Antitrypsin, Resolution, B-Cell Differentiation Factor-2, Membranes, IFN-beta 2, Mediation, Macrophage-Derived, systema genitale femininum, Liver Thiol Proteinase Inhibitor, Women's Groups, HEK293, Mucous, Membrane, gynaecological tissue, Protein Gene Products, Serpin Peptidase Inhibitors, DmelCG7128, HIV-I, Hybridoma, Therapeutic, Short peptide from AAT, concentration, alpha 1-Proteinase, TAF8, Type II, Tnfsf1a0trueSerpin, Cystatin as Novel Correlates of HIV-1 Resistance in the Cervicovaginal Mucosa of Sex WorkersSat Nov 23 04:32:00 GMT 2013MSV00007850621973077