Hepatitis C virus has evolved to invade and hijack the basic machinery of the human liver cell to ensure its survival and spread. Researchers at the University of North have discovered how hepatitis C binds with and repurposes a basic component of cellular metabolism known as a microRNA to help protect and replicate the virus.
In a paper published online in the Proceedings of the National Academy of Sciences Dec. 17, researchers in the laboratory of Stanley M. Lemon, MD, professor of medicine and microbiology and immunology and member of UNC Lineberger Comprehensive Cancer Center, the Center for Translational Immunology, and the UNC Center for Infectious Disease, outline the critical role the microRNA known as miR-122 plays in the life cycle of the hepatitis C virus.
A chronic blood-borne virus that attacks the liver, hepatitis C infects more than four million in the United States and more than 130 million worldwide. Deaths from the infection surpass those due to HIV/AIDS in the U.S. The virus is currently the leading factor in liver transplantation and a major cause of liver cancer, the third most fatal cancer worldwide and the ninth most deadly in the United States. Chronic hepatitis virus infections factor into more than two-thirds of liver cancer deaths.
"There is no cancer in the United States that is increasing in incidence as fast as liver cancer, and that is because of hepatitis C," said Dr. Lemon.
One question has been why hepatitis C virus specifically targets the liver. The research of Dr. Lemon and his colleagues points to the interaction between the hepatitis virus and miR-122 as the explanation.
The human genome contains around 1,000 microRNAs, strands of cellular material that play a diverse role in regulating gene expression and cellular metabolism. In a healthy liver cell, the microRNA miR-122 regulates the activity and decay of numerous cellular RNAs responsible for the production of proteins. It normally functions to block protein expression or to promote degradation of RNAs in the cell. The hepatitis C virus genome is entirely RNA, but miR-122 acts on it in a completely different manner - stabilizing it and enhancing its ability to produce viral proteins. In effect, it promotes and protects the invader.
"MicroRNAs almost always promote the degradation of cellular RNAs. This is actually stabilizing the viral RNA," said Dr. Lemon.