Stock, Jennifer L.
(2014)
Factors associated with the control of SIVsab infection in baboons (papio papio).
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Background. Understanding the mechanisms of simian immunodeficiency virus (SIV) emergence in a new host is a major public health priority of HIV research, as both HIV-1 and HIV-2 emerged through cross-species transmissions from their respective chimpanzee and sooty mangabey (SM) hosts. We therefore studied the factors associated with the fate of cross-species transmitted SIV infection to a new host by comparing and contrasting controlled and progressive cross-species transmitted SIV infections in an African non-human primate (NHP), the Guinea baboon (Papio papio). Baboons, a non-natural host of SIV, were previously reported to carry SIVagm from African green monkeys (AGMs) in the wild and to progress to AIDS when experimentally infected with SIVsmm from SMs.
Methods. Ten baboons were intravenously infected with either SIVagmSab, the virus naturally infecting the sympatric AGMs (Chlorocebus sabaeus) or SIVsmm that naturally infects SMs (Cercocebus atys). The impact of intrinsic immunity on SIV infection was assessed by (i) monitoring temporal changes in the host restriction factor (HRF) (APOBEC3G, Trim5a, SAMHD-1, tetherin and MX2) expression in lymph nodes (LNs) by immunohistochemistry (IHC) and (ii) virus evolution through single genome amplification and sequencing.
Results. Upon exposure to SIV, the viral loads (VLs) peaked at 10-14 days postinfection (dpi). Peak VLs were 2-3 logs lower in SIVsab infected baboons, who controlled the virus to undetectable levels at 28-42 dpi and then through follow-up. Conversely, SIVsmm infection was persistent throughout the follow-up and two out of four SIVsmm infected baboons showed signs of disease progression. IHC quantification revealed an increase in the expression of individual HRFs in the LNs from SIVsab infected controller baboons. Conversely, HRF expression was virtually unchanged in SIVsmm-infected baboons and in AGM natural hosts. SIV quasispecies characterization identified a mutation rate similar to that observed in the natural host in baboons infected with SIVsmm and baboons infected with SIVsab.
Conclusions. Our results demonstrate that combined rather than individual action of HRFs is the major determinant of the outcome of SIV infection upon cross-species transmission. Therefore, approaches aimed at developing new animal models for HIV research should overcome the overall intrinsic immunity instead of focusing on individual factors.
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| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
29 September 2014 |
| Date Type: |
Publication |
| Defense Date: |
14 July 2014 |
| Approval Date: |
29 September 2014 |
| Submission Date: |
22 July 2014 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 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: |
nonhuman primate model, cross species transmission, baboons, SIV, HIV,Host restriction factors, tetherin, SAMHD1, MX2, APOBEC3g, trim5a |
| Date Deposited: |
29 Sep 2014 20:52 |
| Last Modified: |
15 Nov 2016 14:24 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/23044 |
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