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(Unpublished)
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
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| 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: |
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: |
01 Jan 2021 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/33671 |
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