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Influence of behavioral exposures on microRNA regulation in HIV-1 associated neurocognitive disorder (HAND)

Satram, Archana (2015) Influence of behavioral exposures on microRNA regulation in HIV-1 associated neurocognitive disorder (HAND). Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

HIV-1 positive individuals demonstrate a wide variety of comorbidities based on their genetic makeup and their behavioral factors. Differentiation of gene expression caused by behavioral factors such as smoking of tobacco, consumption of alcohol and illicit drug use have been shown to occur through miRNA and can have additive and adverse effects on the co-morbidities associated with HIV-1 infection. Here we try and identify the miRNA that cause the gene regulation and its effects on the progression to HIV-1 associated neurocognitive disorder (HAND) by performing a cross sectional study on miRNA regulation and its downstream effects.
The MACS provided information on all the subjects used in this study. The samples collected were divided based on their infection and cognitive status, resulting in three categories, uninfected controls, HIV-1 positive/dementia negative and HIV-1 positive/ dementia positive. The term dementia was used to identify an individual with any neurocognitive impairment regardless of the actual impairment. The individuals in each category were further divided based on their behavioral habits, smokers, non-smokers etc. The miRNA was obtained from PBMCs of the selected individuals and quantified using TaqMan real time PCR assays. Computational analysis was used to find the miRNA that was significantly regulated by performing inter and intra comparisons within the established categories.
Comparison of miRNA’s in controls vs. HIV-1 positive/dementia negative subjects resulted in a majority of miRNA’s being up-regulated in all variables (smoking, alcohol consumption, pot use). Whereas comparison of miRNA’s in controls vs HIV-1 positive/dementia positive and HIV-1 positive/dementia negative vs. HIV-1 positive/dementia positives resulted in a majority of miRNA’s being down-regulated in all variables. This anomaly shows that HAND is somehow effecting miRNA, mostly by down-regulation.
There were also a large number of miRNA that were common in all variables when comparing controls vs. HIV-1 positive/dementia negative individuals and HIV-1/dementia negative vs. HIV-1 positive/dementia positive individuals. This commonality shows that either HIV-1 alone or in conjugation with the behavioral factors is causing regulation of certain miRNA. This information provides the bases to further explore the possibilities of using miRNA’s as biomarkers for diagnosis and treatment of HIV-associated neurological disorders.
Public Health Implications: The major public health significance projected to come from this study include the identification of early biomarkers in patients who are prone to develop cognitive disorders and identification of mechanisms underlying the development of HAND, which may lead to identification of new drug targets. In the long term, this knowledge may yield novel therapeutic interventions for the treatment of cognitive disorders and antivirals targeting CNS compartments.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Satram, Archanaars189@pitt.eduARS189
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorAyyavoo, Velpandivelpandi@pitt.eduVELPANDI
Committee MemberBarchowsky, Aaronaab20@pitt.eduAAB20
Committee MemberRinaldo, Charles R.rinaldo@pitt.eduRINALDO
Date: 28 January 2015
Date Type: Publication
Defense Date: 1 December 2014
Approval Date: 28 January 2015
Submission Date: 24 November 2014
Access Restriction: 3 year -- Restrict access to University of Pittsburgh for a period of 3 years.
Number of Pages: 50
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MPH - Master of Public Health
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: HIV, HIV-associated neurocognitive disorder, miRNA
Date Deposited: 28 Jan 2015 15:00
Last Modified: 15 Nov 2016 14:25
URI: http://d-scholarship.pitt.edu/id/eprint/23632

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