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Variation in Six Innate Imune Genes Does Not Determine Protective Immunity Against SIV in Rhesus Macaques

Gleeson, Blair (2012) Variation in Six Innate Imune Genes Does Not Determine Protective Immunity Against SIV in Rhesus Macaques. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

HIV vaccine trials in humans have shown variability in vaccine responses among individuals. The SIV:macaque model can be used to understand the outcome of HIV vaccine trials in humans, specifically, the role of the innate immune system in inducing protective immunity. CXCL13, CCL20, CCL1, CCL2, CCL5, and TRIM5α, molecules of the innate immune system, were selected as part of a study into the relationship between these molecules and vaccine response. Sequence variation in the innate immune genes was determined in 25 rhesus macaques that were part of a SIV vaccine trial, a multiple low dose exposure study, or a control group. PCR primers were designed, based on the published rhesus macaque genome, to amplify approximately 2 kilobases of promoter region and the exons of the genes. Each amplicon was sequenced in at least 8 animals, and the sequences were visually screened for single nucleotide polymorphisms (SNPs). Numerous SNPs were detected in all of these genes. Statistical analysis showed that there was no correlation between polymorphisms in these genes and protection against SIV challenge. Copy number variation (CNV) was also examined in these genes using either custom TaqMan copy number assays or SYBR Green assays and quantitative real-time PCR. The results of the TaqMan assay indicate that CXCL13 demonstrates CNV. Genetic variation in these innate immune genes is likely not important in rhesus macaque response to SIV challenge, although larger studies are needed to provide more definitive results. The public
Health significance of this study is that understanding genetic factors that influence macaque responses to vaccination or SIV challenge will help us to understand HIV in humans with the goal of developing a more effective vaccine and the ability to predict individual’s susceptibility to disease or response to vaccination.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Gleeson, Blairbmg50@pitt.eduBMG50
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorMartinson, Jeremyjmartins@pitt.eduJMARTINS
Committee MemberReinhart, Toddreinhar@pitt.eduREINHAR
Committee MemberMurphey-Corb, Michaelmcorb@pitt.eduMCORB
Date: 2 July 2012
Date Type: Publication
Defense Date: 29 March 2012
Approval Date: 2 July 2012
Submission Date: 20 April 2012
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 78
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: HIV, SIV, rhesus macaque, SNPs, CNV
Date Deposited: 02 Jul 2012 14:13
Last Modified: 15 Nov 2016 13:57
URI: http://d-scholarship.pitt.edu/id/eprint/11959

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