Interaction of Hepatitis C Viral Proteins with Cellular Oncoproteins in the Induction of Liver Cancer

Hepatitis C virus infection is a major health problem all over the world. A large proportion of patients infected by HCV develop liver cirrhosis or cancer. However, the mechanism(s) remain to be elucidated. Since HCV does not carry any known oncogene, it is thought that interaction between virally encoded proteins and host proteins is responsible for carcinogenesis. Many crucial interactions between HCV-encoded proteins and host proteins have been reported. In this review we focus on the interaction of viral proteins with important regulators of cell cycle—oncoproteins YB-1, p53, and cyclin D1—which play a major role in cell proliferation, apoptosis, DNA repair, and genomic stability. Genetic variants of HCV accumulate in patients and alter these interactions of host cell proteins. It is a battle between the virus and host and the final outcome depends on the winner; if the host succeeds in clearing the virus the patient may not develop serious liver diseases. On the other hand, if the virus dominates by evolving quasispecies which code for altered proteins that interact differently with host proteins, or induce mutations in host protooncogenes, then the patient may develop liver cirrhosis and/or liver cancer. 1. Introduction Hepatitis C virus (HCV) infection is a major health problem and it appears that about 170 million people worldwide (about 2.0% of world population) are chronically infected and more than 350,000 people die every year from hepatitis C-related liver diseases [1]. It is estimated that about 3 to 4 million new cases are added each year. In Africa the prevalence is the highest and in some countries like Egypt about 15% of the people are infected [2, 3]. Initially HCV does not cause any serious disease but in about 80% of the infected people the virus establishes a chronic infection that leads to the more severe form of liver diseases—primarily cirrhosis and hepatocellular carcinoma (HCC). A large proportion of these chronic carriers (10 to 20%) may end up with cirrhosis and/or HCC over a period of 10 to 20 years after infection. In the USA alone, more than 165,000 HCV-infected people will die of liver diseases or HCC in this decade [4]. Thus, both disease burden and economic burden worldwide are extremely high. Although direct acting drugs are effective in controlling HCV infections, already globally more than 170 million people were infected; a large number of these high risk patients will develop cirrhosis and HCC. Therefore, understanding the interactions between viral proteins and host cell proteins is very important to develop