Author(s)

Jacob J. Bruckner

Graduation Year

2012

Date of Thesis Acceptance

Fall 5-9-2012

Major Department or Program

Biochemistry, Biophysics and Molecular Biology

Advisor(s)

Severine Groh

Abstract

The Hepatitis C Virus, the cause of hepatitis C in humans, affects 170 million people worldwide. Chronic hepatitis, present in up to 85% of patients, often results in liver failure, cirrhosis, or hepatocellular carcinoma, making Hepatitis C the largest co ntributor to liver transplants in the world. Hepatitis C Virus is a negative strand RNA virus with a genome of 10,000 nucleotides that encodes a polyprotein that is post - translationally spliced into 10 individual proteins. The p7 protein, a 63 amino acid long peptide, oligomerizes in the endoplasmic reticulum to form a hexameric ion channel crucial for viral assembly and virion release, although its exact mechanism of action is unknown. This study examined the genetics of p7 in 30 virus infected patients and 15 HIV co - infected patients by cloning and sequencing the p7 gene from serum extracts and liver biopsies. Amino acid sequences were analyzed and the conservation of sequences was compared using d N/ d S ratios across all patients and different disease s tages. Conservation of certain residues were also analyzed and used in coordination with current research to propose potential functions and structures of those residues. There was no significant variation in the conservation of the p7 gene between mild and severe disease patients, however, a significant correlation was observed between the conservation of the gene sequence between mild and severe disease patients amongst HIV co - infected patients, suggesting additional purifying stabilization. This stud y examines the genetics of HCV p7, suggests candidate residues for biochemical analysis, and proposes roles for residues S21, C27, K33, R35, P38, P49, and P58, key amino acids necessary to maintain proper p7 structure and function.

Page Count

68

Subject Headings

Hepatitis virus -- United States, Hepatitis C virus, Hepatitis C -- Genetics, p7 protein‚ Hepatitis C virus, Viral proteins, HIV (Viruses), Liver -- Biopsy, Amino acids, Disease -- Microbiology, Mutation (Biology), Coinfection, Whitman College 2012 -- Dissertation collection -- Biophysics, Biochemistry, and Molecular Biology

Permanent URL

http://hdl.handle.net/10349/1116

Document Type

Public Accessible Thesis

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