Boggs, Emerson Ailidh
(2021)
Characterization of HIV-1 capsid-binding host proteins during infection.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
The human immunodeficiency virus type 1 (HIV-1) capsid is an assembly of over 1,500 capsid (CA) monomers that encapsulates the viral RNA genome. After infection of the cell, this structure dissociates in a process termed uncoating to reveal the reverse transcribed genome that must be integrated into the host cell genome for productive infection. The HIV-1 capsid interacts with a number of host proteins during capsid trafficking and nuclear import in the cell. This study characterizes the importance of cellular localization of capsid-binding host proteins that have been implicated in HIV-1 infection. First, the microtubule motor protein kinesin, a mediator of capsid trafficking during disassembly, was depleted in cells, which was associated with inhibition of HIV-1 infectivity. An inhibitable, fluorescently-tagged kinesin construct was successfully introduced into these kinesin-depleted cells. Second, the re-localization of cleavage and polyadenylation factor 6 (CPSF6) to the cytoplasm impacts HIV-1 capsid trafficking and infectivity. As cyclophilin A (CypA) binding was shown to prevent cytoplasmic CPSF6 binding to HIV-1 capsid, localization of CypA was evaluated and found to differ between HIV-1 target CD4+ T cells and macrophages, which correlates to disparate findings on capsid uncoating dynamics during infection of these cells.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
12 May 2021 |
| Date Type: |
Publication |
| Defense Date: |
20 April 2021 |
| Approval Date: |
12 May 2021 |
| Submission Date: |
11 May 2021 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
66 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
HIV capsid CPSF6 CypA Virology |
| Date Deposited: |
12 May 2021 16:30 |
| Last Modified: |
12 May 2021 16:30 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/41064 |
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