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

Geert Van Raemdonck, Geert Zegels, Edmond Coen, Bea Vuylsteke, Wim Jennes, Xaveer Van Ostade

Research output: Contribution to journalA1: Web of Science-article

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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.

Original languageEnglish
JournalVirology
Volume458-459
Pages (from-to)11-21
Number of pages11
ISSN0042-6822
DOIs
Publication statusPublished - 2014

Keywords

  • Viral diseases
  • HIV-1
  • AIDS
  • In vivo
  • Resistance
  • Vagina
  • Seronegativity
  • Exposure
  • Proteomics
  • Proteins
  • Protease inhibitors
  • Myeloblastin
  • Serpin A5
  • Regulation
  • Côte d'Ivoire
  • Africa-West

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