Biomedical Sciences ETDs

Publication Date

7-1-2011

Abstract

Human immunodeficiency virus type 1 (HIV-1) chronically infects approximately 30 million people worldwide. HIV-1 has become one of the most difficult viral infections to treat due to its high mutability and emerging drug resistance. Critical to our development of more effective therapeutic treatments, we must better understand the HIV life cycle in order to reveal better targets for drug development. Thus, the purpose of this work was to investigate the role of autophagy, a cellular homeostatic mechanism capable of eliminating intracellular pathogens, in HIV-1 infection of two relevant hosts, the human and the Old World non-permissive primate, the rhesus macaque. The ability of autophagy to eliminate HIV-1 in these two species was compared with the objective of identifying why rhesus macaques efficiently eliminate HIV-1 and humans do not. Here we report that human cells have lost autophagic protection against HIV, and identify a role for autophagy in supporting HIV-1 biogenesis and egress from human macrophages. We further identify the rhesus macaque restriction factor, rhesus TRIM5α, as a major player in targeting HIV-1 for degradation through p62-dependent recognition and capture by the autophagy machinery.

Keywords

autophagy, HIV, Nef, RhTRIM5╬▒

Sponsors

American Foundation for AIDS Research, National Institutes of Health, Bill and Melinda Gates Grand Challenge Explorations, NIH IDIP predoctoral training program, Vojo Deretic, PhD, and The Department of Molecular Genetics and Microbiology, University of New Mexico HSC

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Advisor

Deretic, Vojo

First Committee Member (Chair)

Hartley, Rebecca

Second Committee Member

Hu, Chien-An

Third Committee Member

Chackerian, Bryce

Fourth Committee Member

Antonito, Panganiban

Fifth Committee Member

Peabody, David

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