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.

Discovery of Antimicrobial Peptides in Cervical‐Vaginal Fluid from Healthy Nonpregnant Women via an Integrated Proteome and Peptidome Analysis

“…These protease inhibitors include 22 members of the serpin superfamily and two serine protease inhibitor Kazal type (SPINK) members, known to inhibit various serine proteases such as members of the kallikrein‐related peptidase family. The clinical importance of understanding protease activity in CVF was recently highlighted, as it was shown that resistance to HIV in CVF is dependent on the balance between serine proteases and serine protease inhibitors …”

Quantitative body fluid proteomics in medicine — A focus on minimal invasiveness

“…The proteomic analysis of vaginal fluid can provide more information about the pathophysiological conditions affecting the female genital tract [118,119]. 63 potential biomarkers for pregnancyrelated problems such as intra-amniotic inflammation [112,120] and preterm labour/preeclampsia [121][122][123][124][125], cervical cancer [126] and HIV infection [127] were identified (Table 6) using quantitative proteomics techniques and six biomarkers were validated.…”

A Quantitative Proteomics Approach to Clinical Research with Non-Traditional Samples

“…An iTRAQ based study was conducted to analyze CFV from HIV-exposed seronegative individuals (HESN) that were at high risk compared to low risk (HESN) and HIV positive patients. The research revealed that Serpin A5 was up regulated and Myeloblastin was downregulated in high risk HESN when compared to that in the other groups [66]. Further study into the mechanism behind HIV resistance and development of treatments is recommended [66].…”

“…The research revealed that Serpin A5 was up regulated and Myeloblastin was downregulated in high risk HESN when compared to that in the other groups [66]. Further study into the mechanism behind HIV resistance and development of treatments is recommended [66]. …”