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Understanding the role of astrocytes in HIV-1 neuropathogenesis: novel strategies to target astrocyte function and HIV-1 associated neurocognitive disorder

Jain, Ruhee (2018) Understanding the role of astrocytes in HIV-1 neuropathogenesis: novel strategies to target astrocyte function and HIV-1 associated neurocognitive disorder. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

HIV-1 infection is associated with changes in cognition and neuronal function, known as HIV-associated neurocognitive disorder (HAND), with the most severe form resulting in dementia. Astrocytes in the frontal cortex have a critical role in neuropathogenesis induced by HIV-1 as they undergo “astrocytosis” that is commonly found in HAND subjects. Astrocytes are a type of glial cells located in the central nervous system and are targets for HIV-1 infection, though it is defective in producing replication competent viruses. However, the infected astrocytes are capable of producing viral proteins and are reactivated. These star-shaped cells serve many functions, such as providing structural and metabolic support to nearby neurons, and have a central role in the maintenance of the neuronal synapse and the blood brain barrier. Astrocytes undergo structural and functional transformations in the occurrence of CNS infection, but it is unclear whether this plays a role in HIV-1 pathogenesis. Host cellular factors including microRNAs have been suggested to regulate the balance between neuroprotective and neurotoxic factors in astrocytes. While combination antiretroviral therapy (cART) can be used to treat viral replication, these drugs do not penetrate the central nervous system, and therefore treatment of infection within the brain is limited. Thus, identifying new therapeutics is important to reduce the burden of HAND, which has great public health significance.
We have previously identified candidate miRNA that are known to have potential neuroprotective effects. In my project, I evaluated whether these miRNA have a role in regulating virus replication and/ or virus reactivation in astrocytes.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Jain, Ruheeruj6@pitt.eduRUJ6
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorAyyavoo, Velpandivelpandi@pitt.edu
Committee MemberMartinson, Jeremyjmartins@pitt.edu
Committee MemberPadiath, Quasarqpadiath@pitt.edu
Date: 30 January 2018
Date Type: Publication
Defense Date: 13 December 2017
Approval Date: 30 January 2018
Submission Date: 1 January 2018
Access Restriction: 3 year -- Restrict access to University of Pittsburgh for a period of 3 years.
Number of Pages: 51
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-1, miRNA, astrocytes
Date Deposited: 30 Jan 2018 22:37
Last Modified: 30 Jan 2018 22:37
URI: http://d-scholarship.pitt.edu/id/eprint/33671

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