Defense Date

3-15-2011

Graduation Date

Spring 2011

Availability

Immediate Access

Submission Type

dissertation

Degree Name

PhD

Department

Chemistry and Biochemistry

Committee Chair

Mihaela-Rita Mihailescu

Committee Member

Ellen Gawalt

Committee Member

David Seybert

Committee Member

Bruce Armitage

Keywords

Genomic dimerization, Hepatitis C virus, Kissing complex, PNA, RNA, Therapeutic

Abstract

Hepatitis C, a life threatening disease, caused by the hepatitis C virus (HCV) currently affects over 170-200 million people worldwide (~3% of global human population), more than five times the percentage of total HIV infections. HCV infection has been shown to be a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma and is the leading cause of liver transplantation in the U.S. HCV has escaped every therapeutic target to date by means of its error-prone RNA polymerase, which allows it to mutate prolifically. The current standard anti-HCV therapy, which is pegylated interferon a combined with ribavirin, is difficult to tolerate, and more than 50% of HCV patients are refractory to it. No protective vaccine or therapeutic antibody is available, making the need for the development of an efficacious immunoprophylactic and therapeutic agent imperative. HCV is an enveloped virus with a positive sense RNA genome of ~9.6 kilobases (kb), which carries a large open reading frame (ORF), flanked by 5'- and 3'- untranslated regions (UTRs). Interestingly, within the highly mutational HCV RNA, there are a limited number of 100% conserved and functionally vital motifs, located in the 5' UTR, coding region and in the 3' UTR. Within the HCV genome, these motifs have been proposed to be involved in multiple exclusive interactions with each other and furthermore, these interactions have been demonstrated to be essential for HCV replication and/or translation of the viral proteins.

Format

PDF

Language

English

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