Almost 4 million people are infected with hepatitis C virus (HCV) in the United States alone, with 170 million infected worldwide. It is the leading cause of liver transplantation in the US. Although infection is initially asymptomatic, HCV often leads to chronic liver disease, cirrhosis, and/or liver cancer. Many cases are treatable with combination therapy (interferon, ribavirin, and new protease inhibitors), but efficacy is dependent on the infecting strain and there is currently no vaccine. Without more effective antiviral and immunological treatments, the Centers for Disease Control and Prevention (CDC) predicts that deaths due to HCV will double or triple in the next 15 to 20 years due to prolonged disease and continued spread. The high prevalence of infection, lack of highly effective HCV-specific inhibitors, and poor response rate to the current treatment underscore the importance of developing new therapeutic strategies. The mechanism of viral entry is an important subject of study with respect to preventing and treating infection. Two of the four HCV structural proteins, envelope 1 (E1) and envelope 2 (E2), heterodimerize on the surface of the virion. Experimental evidence supports the roles of E1 and E2 in receptor binding, virus-cell fusion, and entry into the host cell. These factors make E1 and E2 key determinants of pathogenicity and optimal targets of vaccine design. We hypothesize that a thorough biophysical understanding of E2, as well as improvements in the available biochemical tools for the study of HCV E2 will provide a significant advancement in the understanding of viral infection.Ph. D.Includes bibliographical referencesby Jillian L. Whidb
