For the first time, scientists have replicated hepatitis C virus (HCV) in the laboratory. The ability to replicate HCV in cell cultures will allow researchers to study better the life cycle and biology of this virus and to test potential antiviral compounds, which may lead to new therapies for the liver disease that results from infection with HCV. Scien-tists at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), one of the National Institutes of Health (NIH), conducted the study (Proceedings of the National Academy of Sciences, Feb. 15, 2005).
“Our model system produced viral particles that have all the properties of the whole virus,” said T. Jake Liang, MD, chief of the liver diseases branch of the NIDDK and co-author of the study. “This evidence, together with an analysis of the replicated viral RNA, supports a conclusion of viral replication and production.”
The NIDDK group used a strain of HCV that would have applications to the greatest number of people—genotype 1, the major type of HCV of human infections worldwide and the type most resistant to current therapies. The NIDDK scientists found evidence of HCV proteins and HCV RNA within the human liver cells in the culture. Electron microscopy showed evidence of high levels of viral particles resembling the fully formed HCV outside of the human liver cells in the culture medium. The researchers believe that the HCV construct contained within the human liver cells behaved like a true HCV infection by producing fully formed copies of the virus and releasing them from the host cell into the culture medium. Further testing is needed before the researchers can determine if the viral particles produced in this system are in fact infectious. Also, this system only represents the tail end of the viral life cycle—viral replication, assembly, and release from host cells. Another HCV model system is needed to show the beginning stages of the viral life cycle—viral entry into host cells and viral activity in the host cell before replication.
HCV is a small, enveloped, single-stranded RNA virus in the family Flaviviridae. HCV is a major cause of liver disease in the United States and the world. One in a series of hepatitis viruses, HCV accounts for about 15% of acute hepatitis cases, 60% to 70% of chronic hepatitis cases, and up to 50% of cases of cirrhosis, end-stage liver disease, and liver cancer. Almost 4 million Americans (1.8%) have antibodies to HCV, indicating ongoing or previous infection with the virus. Approximately 10,000 to 12,000 deaths each year in the United States are due to HCV.
(Source: NIH NEWS, Feb. 22, 2005)
