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Characterization of HIV-1 capsid-binding host proteins during infection

Boggs, Emerson Ailidh (2021) Characterization of HIV-1 capsid-binding host proteins during infection. Master's Thesis, University of Pittsburgh. (Unpublished)

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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
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Boggs, Emerson Ailidhemersonailidh@gmail.comEAB153
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairAmbrose, ZandreaZaa4@Pitt.eduzaa4
Committee MemberMattila, JoshuaJMattila@Pitt.edujmattila
Committee MemberKane, MelissaKaneMe@Pitt.edukaneme
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: Graduate 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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