Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Barr, Stephen

Abstract

Interferons that trigger the release of innate antiviral proteins are a vital immune defense mechanism against viruses such as HIV-1. HERC5, an interferon stimulated protein inhibits HIV-1 replication through two independent mechanisms: inhibiting export of HIV-1 RNA through the Rev-dependent pathway and blocking an early step in the assembly of the virion. HERC5 is an antiviral protein yet individuals infected with HIV fail to control the infection. This can be due to viral antagonist mechanisms which counteract the function of restriction factors. Using a viral particle release assay, I discovered HIV-1 Env and Vpu can function as potential antagonists to HERC5. Furthermore, HIV-1 Env sequences derived from infected patients suggested that the antagonistic effect might be dependent on sequence dependent. Altogether, our data will be utilized to identify a novel target for the design of small molecule inhibitors to thwart the viral antagonism of HERC5.

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