The findings, reported in the Dec. 7 issue of The Journal of Biological Chemistry, may give scientists a target for future development of treatments for the virus.
In the early stages of a Hepatitis C Virus (HCV) infection, the researchers found, the virus binds to receptors on the liver cells’ surface, activating PI3K and AKT, two proteins that control cell growth and metabolism, and which allow HCV to enter liver cells.
“When these two protein factors are activated, they trigger a cascade of reactions, altering the physiology of infected cells,” said corresponding author and lead researcher James Ou, professor of molecular microbiology and immunology at the Keck School of Medicine of USC. “Later, by continuing to disturb this pathway, the virus may sensitize the liver cells to eventually become cancerous.”
First author of the findings was Zhe Liu, a postdoctoral research associate in Ou’s lab. Serving as co-investigators were Keck School faculty Keigo Machida, assistant professor of molecular microbiology and immunology, and Michael Lai, Distinguished Emeritus Professor of Microbiology and Immunology, and Neurology.
There are 4 million carriers of HCV in the United States. People often don’t know they have the virus until they already have some liver damage, which can take many years to develop. In time, the virus can lead to cancer, organ failure and cirrhosis, a chronic, degenerative condition.
Some 20 percent of HCV patients will develop severe liver cirrhosis and may require liver transplantation, Ou noted. About 5 percent develop liver cancer after 20 to 30 years.
Ou has been studying HCV for 20 years and Hepatitis B virus for 30 years. The most recent study reflects his long-term interest in understanding the interactions between these two viruses and their host cells, and how they cause liver cancer.
“The next step, which we’ve just begun, is to understand how the activation of the PI3K-AKT pathway allows the [HCV] virus to enter the cell,” Ou said. “This research has led to the identification of a novel target for the development of new anti-HCV drugs. Compounds that disrupt the PI3K-AKT pathway are expected to prevent the virus from entering liver cells, causing the virus to disappear.”
The research was supported by National Institutes of Health grants.