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Simian Immunodeficiency Virus Pathogenesis And The Gastrointestinal Tract

Malzahn, Jessica M (2011) Simian Immunodeficiency Virus Pathogenesis And The Gastrointestinal Tract. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

It has been shown that HIV/SIV preferentially replicates in the gut associated lymphoid tissue (GALT) which leads to immune activation and disease progression. Different sections of the gastrointestinal (GI) tract have unique biological functions with specialized lymphoid tissue composition and distribution, which may contribute differently to viral pathogenesis. We hypothesize that the GALT serves as an active viral replication site during the acute and AIDS stages of HIV/SIV infection and as a viral reservoir in long-term non-progressors (LTNP) and antiretroviral therapy (ART) treated individuals; this viral replication results in local immune activation which contributes to disease progression. The RNA and DNA were isolated from tissues along the GI tract of uninfected and SIV infected rhesus macaques in different disease stages with or without ART. Real-time PCR was utilized to measure viral RNA and DNA, and mRNAs of CD4, TNF-α, IL-6, IL-1β, and MyD88. Our results showed that SIV DNA/RNA were detected in all GI tissues from infected monkeys regardless of the disease stage and drug intervention. However, the viral load distribution profile in the GI tract varied from monkey to monkey. Despite the undetectable viral load in peripheral blood, both viral RNA and DNA were detected in GI tissues of ART treated monkeys. Compared to the uninfected monkeys, low levels of CD4 mRNA were detected in SIV infected monkeys, particularly LTNP. There is a positive association between viral load and mRNA levels of TNF-α, IL-6, and MyD88 in the stomach and duodenum. However, no association was observed between viral loads and IL-1β mRNA levels in any of the GI tissues examined. Data from this study indicates that the entire GI tract serves as a SIV replication site in all stages of infection, which leads to pro-inflammatory cytokine production and local inflammation. This study reveals the importance of the entire GI tract in HIV/SIV pathogenesis. Especially, in ART treated individuals with undetectable viral loads in blood, active viral replication in gut tissue may lead to development of drug resistant variants and faster progression to AIDS. This will have a profound impact on clinical intervention and public health as a whole.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Malzahn, Jessica Mjmalzahn@hotmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairChen, Yuecheny@pitt.eduCHENY
Committee MemberBauer, Anthonytbauer@pitt.eduTBAUER
Committee MemberGupta, Phalgunipgupta1@pitt.eduPGUPTA1
Date: 29 June 2011
Date Type: Completion
Defense Date: 20 April 2011
Approval Date: 29 June 2011
Submission Date: 4 April 2011
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
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: ART; gastrointestinal tract; inflammatory cytokines; SIV
Other ID: http://etd.library.pitt.edu/ETD/available/etd-04042011-183822/, etd-04042011-183822
Date Deposited: 10 Nov 2011 19:34
Last Modified: 15 Nov 2016 13:38
URI: http://d-scholarship.pitt.edu/id/eprint/6749

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