| Infection with Hepatitis C Virus (HCV) often becomes chronic and can lead to cellular transformation and ultimately hepatocellular carcinoma in 5% of individuals infected. This phenomenon triggers considerable interest in the analysis of potential interactions between individual HCV proteins and host cell proteins regulating cell growth. Recently, the potential of NS3 protease to elicit a malignant response has been mildly explored. Viral proteases are known to affect cellular metabolism. Without regulatory restrictions, NS3 has the ability to not only disrupt growth pathways by direct protein-protein interaction, but also to degrade regulatory proteins, thereby influencing the initial stages of cellular transformation. It was found that expression of NS3 in Huh 7.0 cells could activate several oncogene - related pathways namely NFkB and c-fos. Detection was measured via chemiluminescence and mammalian two hybrid assays. I have currently narrowed down the region of NS3 responsible for this up-regulation to approx. 300 amino acids. Identification of this motif will not only provide powerful insight into the host factors involved in HCV protein interaction but will ultimately serve to provide therapeutic potential in treatment of hepatocellular carcinoma. |
