Date of Award


Degree Type


Degree Name

Master of Science (MS)


Microbiology and Immunology


Human immunodeficiency virus 1 (HIV-1) is a lentivirus that progresses to acquired immunodeficiency syndrome (AIDS). The protein TRIM5alpha from rhesus macaques (rhTRIM5alpha) restricts HIV-1 by blocking infection after entry of the virion into cells. Treatment of rhTRIM5alpha expressing cells with inhibitors to a cellular degradation pathway, the proteasome, partially relieves restriction but does not inhibit rhTRIM5alpha protein turnover. The role of a second degradation pathway, the autophagy-lysosomal pathway, in TRIM5alpha mediated restriction has not been explored.

In the present study, we demonstrate that rhTRIM5alpha is degraded by chaperone mediated autophagy (CMA). Inhibition of CMA alters rhTRIM5alpha localization and turnover, while inhibition of other autophagic pathways has no effect. We identify a CMA motif within rhTRIM5alpha that is responsible for lysosomal degradation. We demonstrate that inhibition of lysosomal degradation alters the restriction profile ofrhTRIM5alpha. These studies describe a previously uncharacterized role for CMA degradation in rhTRIM5alpha stability and retroviral restriction.

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