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

• Published in: Virology (New York, N.Y.) N.Y.), 2014-06, Vol.458, p.11-21
• Main Authors: Van Raemdonck, Geert, Zegels, Geert, Coen, Edmond, Vuylsteke, Bea, Jennes, Wim, Van Ostade, Xaveer
• Format: Article
• Language: English
• Subjects: Body Fluids - enzymology; Cervicovaginal fluid; Cote d'Ivoire - epidemiology; Female; Gene Expression Regulation, Enzymologic - immunology; Genetic Predisposition to Disease; HESN; HIV Infections - epidemiology; HIV Infections - immunology; HIV Infections - virology; HIV resistance; HIV-1 - physiology; Human immunodeficiency virus 1; Humans; Infectious Disease; iTRAQ; Myeloblastin; Protein C Inhibitor - chemistry; Protein C Inhibitor - genetics; Protein C Inhibitor - metabolism; Proteomics; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism; Serine Proteases - genetics; Serine Proteases - metabolism; Serpin A5; Sex Workers
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2014.04.015

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.