Griffin, K.R.
(2013)
SIV Escape from Immune Recognition Due to Selection Pressure of Immunodominant CD8+ Epitope GAG-CM9 and TRIM5 Restriction Sites.
Master's Thesis, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
HIV/AIDS has been a major public health focus for more than 40 years. By using the rhesus macaque/SIV model, we are able to learn more about immune response and host genetics than through human study alone.
There is a complex interplay between host and viral factors that determine the course of an HIV/SIV infection. The overall goal of this retrospective study is to analyze the dual evolution of both the immunodominant CD8+ GAG-CM9 epitope and the binding sites for restriction by the host protein TRIM5α that are located on the highly conserved GAG region of the SIV genome. Early and late time points in an SIV infection will be analyzed to determine the favored drivers for viral escape.
In Specific Aim 1, a cohort of 15 Mamu A*01 rhesus macaques was characterized by viral load profile and TRIM5 haplotype. Six animals were “Controllers,” 5 animals maintained and “Intermediate Viral Load,” 3 animals maintained a “High Viral Load,” and 2 animals “Crashed and Burned.” Six animals had the TRIM5TFP/TFP haplotype, 7 animals were classified as TRIM5TFP/Q, and 2 animals were classified as TRIM5Q/Q. No TRIM5CypA allele was found in
the cohort. No statistical significance could be shown between TFP/TFP animals and TFP/Q animals, but there was significance when comparing TFP/TFP and Q/Q.
In Specific Aim 2, the sequence of both early and late time points from an immunotherapeutic trial were compared to the original inoculum. Early time points from the trial showed near complete homology with the inoculum at the residues of interest. Late time points showed that the R98S mutation was important for an animal’s ability to control virus.
No significant mutation occurred at the GAG-CM9 epitope. Mutations at anchor residues did not contribute to an animal’s ability to control virus and showed no correlation with TRIM5 haplotype. However, the polymorphisms in TRIM5 may be contributing to the variation in overall immune response as the avidity with which TRIM5α binds to the viral capsid shows correlation with the strength of innate immune signaling.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
27 June 2013 |
| Date Type: |
Publication |
| Defense Date: |
9 April 2013 |
| Approval Date: |
27 June 2013 |
| Submission Date: |
3 April 2013 |
| Access Restriction: |
3 year -- Restrict access to University of Pittsburgh for a period of 3 years. |
| Number of Pages: |
90 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
TRIM5, TRIM5alpha, Cytotoxic T Lymphocyte, CTL, GAG, CM9, SIV, Mamu A*01, viral escape |
| Date Deposited: |
27 Jun 2013 18:42 |
| Last Modified: |
15 Nov 2016 14:11 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/18507 |
Available Versions of this Item
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SIV Escape from Immune Recognition Due to Selection Pressure of Immunodominant CD8+ Epitope GAG-CM9 and TRIM5 Restriction Sites. (deposited 27 Jun 2013 18:42)
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