Measurement and characterization of HIV inhibitory Clade A Serpins in the cervical mucosa of highly HIV-1 exposed seronegative individuals

dc.contributor.authorRahman, Syeda Sharmin
dc.contributor.examiningcommitteeCarpenter, Michael (Medical Microbiology) Yao, Xiao-Jian (Medical Microbiology) Ho, Emmanuel (Pharmacy)en_US
dc.contributor.supervisorBall, Blake (Medical Microbiology) Plummer, Frank (Medical Microbiology)en_US
dc.date.accessioned2012-01-10T21:54:32Z
dc.date.available2012-01-10T21:54:32Z
dc.date.issued2011-11-04
dc.degree.disciplineMedical Microbiologyen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractObjective: Serpins are serine protease inhibitors that are involved in a wide variety of biological functions in nature. They are known to regulate inflammation processes as well as provide host defense against microorganisms. Recent evidence has associated many types of mucosal serpins with a protective phenotype against HIV infection in women. Our hypothesis is that serpins with known antiviral activity against HIV-1 are correlated with protection in a group of HIV exposed seronegative individuals (HIV-resistant) from the Pumwani sex worker cohort. Study design: Cervico-vaginal lavage (CVL) fluid was collected from 66 HIV-positive, 82 HIV-negative and 84 HIV-resistant sex workers from the cohort. Clinical and epidemiological information was recorded at the time of sample collection. CVL protein levels were determined by BCA assay and serpin (A1 and A3) concentrations by a commercially available ELISA kit. Mucosal serpin concentrations were compared against clinical and epidemiological factors as well as sexual practices. Results: Serpin A1 was significantly higher in the HIV-resistant group compared to the HIV-negative controls (Anova: p=0.0470*). Total concentration of serpin A3 did not reach statistical significance between groups. Serpins did not correlate with age, sexual practices, contraceptive use or number of pregnancies. Serpins were differentially abundant during different stages of the menstrual cycle whereas serpin A1 was elevated during the proliferation phase but not in secretory phase (p=0.0275*). Conclusion: Serpin A1 was correlated with HIV-protection in this group of HESN women. This work will contribute to a more complete understanding of mechanisms of resistance and susceptibility to HIV infection.en_US
dc.description.noteFebruary 2012en_US
dc.identifier.citationA. Burgener et al. Comprehensive Proteomic study identifies serpins and cystatin antiproteases as novel correlates of HIV-1 resistance in the ceervicovaginal mucosa of female sex workersen_US
dc.identifier.urihttp://hdl.handle.net/1993/5065
dc.language.isoengen_US
dc.publisherAmerican Chemical Society (ACS) Publicationsen_US
dc.rightsopen accessen_US
dc.subjectHIV-1en_US
dc.subjectSerpinsen_US
dc.titleMeasurement and characterization of HIV inhibitory Clade A Serpins in the cervical mucosa of highly HIV-1 exposed seronegative individualsen_US
dc.typemaster thesisen_US
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