title: Increased Serpin A5 levels in the cervicovaginal fluid of HIV-1 exposed seronegatives suggest that a subtle balance between serine proteases and their inhibitors may determine susceptibility to HIV-1 infection.
abstract: HIV-exposed seronegative individuals (HESNs) are persons who remain seronegative despite repeated exposure to HIV, suggesting an in vivo resistance mechanism to HIV. Elucidation of endogenous factors responsible for this phenomenon may aid in the development of new classes of microbicides and therapeutics. We compared cervicovaginal protein abundance profiles between high-risk HESN and two control groups: low-risk HESN and HIV-positives. Four iTRAQ-based quantitative experiments were performed using samples classified based on presence/absence of particular gynaecological conditions. After statistical analysis, two proteins were shown to be differentially abundant between high-risk HESNs and control groups. Serpin A5, a serine proteinase inhibitor and Myeloblastin, a serine protease, were up- and downregulated, respectively. Commercially available ELISA assays were used to confirm differential Serpin A5 levels. These results suggest that HIV resistance in CVF of HESNs is the result of a delicate balance between two complementary mechanisms: downregulation of serine proteinases and upregulation of their inhibitors.
authors.affiliation: Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Centre for Proteomics and Mass spectrometry (CFP-CeProMa), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Van Raemdonck
authors.affiliation: Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Centre for Proteomics and Mass spectrometry (CFP-CeProMa), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Zegels
authors.affiliation: Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Centre for Proteomics and Mass spectrometry (CFP-CeProMa), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Edmond
authors.initials: E
authors.lastname: Coen
authors.affiliation: HIV/STI Epidemiology and Control Unit, Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium Projet and RETRO-CI, Abidjan, Côte d׳Ivoire.
authors.forename: Bea
authors.initials: B
authors.lastname: Vuylsteke
authors.affiliation: Laboratory of Immunology, Department of Microbiology, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Jennes
authors.affiliation: Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Centre for Proteomics and Mass spectrometry (CFP-CeProMa), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium. Electronic address: Xaveer.VanOstade@uantwerp.be.
authors.forename: Xaveer
authors.initials: X
authors.lastname: Van Ostade
mesh_terms: D001826:Body Fluids / Q000201:enzymology*; D007560:Cote d'Ivoire / Q000453:epidemiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018046:Protein C Inhibitor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D057057:Serine Proteases / Q000235:genetics / Q000378:metabolism*; D060386:Sex Workers
chemical_list: D018046:Protein C Inhibitor; C534934:SERPINA5 protein, human; D057057:Serine Proteases; D012697:Serine Endopeptidases
keywords: Cervicovaginal fluid; HESN; HIV resistance; Myeloblastin; Proteomics; Serpin A5; iTRAQ