Last year Peter Sarnow, PhD, professor of microbiology and immunology at the Stanford University School of Medicine, identified a previously unknown mechanism that the hepatitis C virus uses to replicate, yielding a promising new approach to combating the disease-causing virus.
According to the World Health Organization, hepatitis C virus infects 170 million people worldwide. About 70 percent of those infected develop liver disease, including cirrhosis and liver cancer. In the United States, it is the most common blood-borne viral infection, killing more than 10,000 people each year. Currently available treatments are expensive and do not work in about half of the cases.
"Normally with an RNA virus like hepatitis C, resistance to antivirals very quickly emerges, so the drug is not effective any more," said Sarnow, who has been studying the virus for years, sorting out how the viral RNA amplifies in cultured liver cells.
In the normal sequence of events, genetic information is stored in DNA and then is copied into RNA, which serves as a template to create proteins. With RNA viruses such as hepatitis C, the genetic information is stored in RNA instead of DNA.
RNA is genetically more unstable than DNA, resulting in the accumulation of many mutations. These mutations allow the virus to outwit the immune system and develop resistance to antiviral medication.
Sarnow's group has shown that a small fragment of RNA found in the liver, known as a microRNA, is necessary for hepatitis C to grow and reproduce. Their work, published in September 2005 in the journal Science, is the first to link the presence of a specific microRNA with a major infectious disease.
When the researchers inactivated the microRNA, called miR-122, the amount of hepatitis C virus RNA was reduced by approximately 80 percent. "The cool thing is that here, an antiviral is encoded by a host function and not by the virus - so it cannot change," said Sarnow. In other words, because the virus needs miR-122 to replicate, there is no way the virus could develop resistance to a strategy that inactivates miR-122.