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Regulation of Neuroinflammatory Factors by Neuroprotective MicroRNAs in HIV-1 Infected Microglia

Amirova, Samira (2020) Regulation of Neuroinflammatory Factors by Neuroprotective MicroRNAs in HIV-1 Infected Microglia. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Despite successful antiretroviral therapy (ART), more than half of individuals living with HIV-1 exhibit HIV-1 Associated Neurocognitive Disorder (HAND). Individuals with HAND experience a spectrum of cognitive, motor, and/or mood dysfunctions. Currently, there are no treatment or prevention methods for HAND. HIV-1 virus enters through the blood-brain barrier (BBB) and establishes infection in CD4+ cells such as macrophages and microglia present in the central nervous system (CNS). Macrophages and microglia are the key targets for HIV-1 in CNS. Infected target cells release inflammatory cytokines and viral proteins that are exposed to neurons. The combination of viral and host factors triggers neuronal damage that results in neurodegeneration, the hallmark of HAND pathology. Identifying new therapeutics is important to reduce the negative effects of HAND, which has great public health significance.
To combat this problem, we propose to target neuroinflammatory factors that have been identified to have a role in the development of HAND using microRNAs (miRNAs). These miRNAs target biological pathways including homeostasis of cellular interaction, regulation of neurotoxic and neuroprotective factors, cell proliferation, and differentiation. In this study, we explore the effects of these candidate miRNAs and their role in regulating the production of neuroinflammatory chemokines and cytokines. By modulating the microglia response to HIV-1 infection, I will be able to understand how normal functioning of microglia in the CNS is interfered by virus infection. Through this knowledge, there will be an increased likelihood of developing novel therapeutic strategies and treatment for neurocognitive disorders.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Amirova, Samirasga16@pitt.edusga160000-0001-7963-090X
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairAyyavoo, Velpandivelpandi@pitt.eduvelpandi
Committee MemberMartinson, Jeremyjmartins@pitt.edujmartins
Committee MemberDi, Peterpeterdi@pitt.edupeterdi
Date: 30 July 2020
Date Type: Publication
Defense Date: 14 April 2020
Approval Date: 30 July 2020
Submission Date: 11 May 2020
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 62
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: microRNA; microglia; HIV-1; virus; immune function; replication; HAND;
Date Deposited: 30 Jul 2020 17:07
Last Modified: 30 Jul 2020 17:07
URI: http://d-scholarship.pitt.edu/id/eprint/38986

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