Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Stephen Barr

Abstract

Herc5 is a potent HIV-1 restriction factor able to restrict HIV-1 by two mechanisms: 1) conjugation of ISG15 to gag polyprotein via E3 ligase activity, and 2) restricting the production of HIV-1 proteins by an unknown mechanism that is independent of its E3 ligase function. Herc5 mutations of the RCCl-like domain (RLD) and Spacer domains were generated to dissect this mechanism. Based on HIV-1 release assays, the RLD is important for preventing the production of viral proteins. Herc5 transfected cells show defects in cell cycle progression at the G2/M phase as well as abnormal nuclear morphology. C994A and ASpacer constructs did not impact these phenotypes. However, ARLD Herc5 constructs had normal cell cycle and nuclear morphology. Based on the results found, the RLD was found to be an important mediator of Herc5 cellular and antiviral activity.

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