HIV-1 and the Nucleolus: A Role for Nucleophosmin/NPM1 in Viral Replication: A Dissertation
Authors
Schmidt, Tracy E.Faculty Advisor
Maria Zapp, PhDAcademic Program
Interdisciplinary Graduate ProgramUMass Chan Affiliations
Program in Molecular MedicineDocument Type
Doctoral DissertationPublication Date
2013-08-21Keywords
Dissertations, UMMSCell Nucleolus
Virus Replication
Nuclear Proteins
HIV-1
Cell Nucleolus
Virus Replication
Nuclear Proteins
HIV-1
Cell Biology
Cellular and Molecular Physiology
Virology
Metadata
Show full item recordAbstract
The nucleolus is a plurifunctional organelle with dynamic protein exchange involved in diverse aspects of cell biology. Additionally, the nucleolus has been shown to have a role in the replication of numerous viruses, which includes HIV-1. Several groups have reported HIV-1 vRNA localization within the nucleolus. Moreover, it has been demonstrated the HIV-1 Rev protein localizes to the nucleolus and interacts with nucleolar proteins, including NPM1. Despite evidence for a nucleolar involvement during replication, a functional link has not been demonstrated. I investigated whether introncontaining vRNAs have a Rev-mediated nucleolar localization step prior to export. Furthermore, I examined whether NPM1 mediates Rev nucleolar localization, participates in Rev function, and/or post-transcriptional events during viral replication. I used coupled RNA fluorescence in situhybridization and indirect immunofluorescence to visualize intron-containing vRNA relative to the nucleolus in the absence or presence of Rev expression. An RNAi-based approach was used to examine the role of NPM1 in Rev function and viral replication in cell lines and primary human macrophages. My research findings support a model for a Rev-independent nucleolar localization step of introncontaining vRNA prior to export. Intriguingly, my results also suggest NPM1 does not participate in Rev nucleolar localization or Rev-mediated vRNA export, as previously proposed. Rather, my findings support a novel role for NPM1, the cytoplasmic localization and utilization of a select class of Rev-dependent vRNAs. Collectively, my findings provide novel insight for a functional role of the nucleolus and NPM1 in HIV-1 replication, which enhances our current understanding of HIV-1 biology.DOI
10.13028/M2MK6VPermanent Link to this Item
http://hdl.handle.net/20.500.14038/32046Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/M2MK6V