Grant: Fellowship - PA: Regional Partnership Program - Newfoundland & Labrador

Hepatitis C virus (HCV) is considered a major global health problem. It infects 170 million people worldwide causing liver cirrhosis and hepatocellular carcinoma. The HCV genome encodes a small protein called p7, but until now, limited information is known regarding the role of p7 in the HCV life cycle. Analysis of this role is considered to be a high priority in HCV biology. The aim of this study is to investigate the role of p7 in the HCV life cycle. In order to do this we created multiple changes covering two thirds of the amino acid sequence of p7 in the background of a complete virus sequence. Analysis of these modified viruses showed that p7 is important for infectious virus production. In addition, we have tested the role of this protein at different stages of the viral life cycle and found that the p7 is not involved in release of the virus from the host cell. We also found that these regions of p7 do not affect the recruitment of the major viral structural protein called core to lipid rich areas of the cell where it is believed the virus forms, and did not affect one of the major viral non-structural proteins called NS3 that is important in viral genome replication. Recently, we found that one of our mutations located in a highly conserved region of p7 known as the cytopalsmic loop affects E2 (envelope protein 2) expression levels; an important structural protein that plays a major role in virus entry into host cells. Thus, we will continue to test how p7 affects E2 protein expression at different stages of the viral life cycle. We will test whether p7 interacts with other viral proteins and determine if it acts as an accessory protein to maintain other viral protein functions. In the bigger picture, the observed effect at the highly conserved region of p7 on the E2 glycoprotein makes p7 a great potential target for antiviral agents. We believe that results from our work will provide important contributions regarding HCV nature and treatment discoveries