Robert Purcell (NIAID)
Rodney Russell (NIAID)
Hepatitis C virus (HCV) infection causes chronic liver disease and is a major global health problem with an estimated 170 million people affected worldwide and 3-4 million new cases every year. Therapeutic advances will be greatly aided by the ability of researchers to successfully replicate and characterize the virus in vitro. The study of HCV replication has, however, been hindered by the lack of an efficient virus culture system. One approach, using cell culture adaptive mutations in the viral RNA has been found to significantly enhance HCV virus production, but it has been difficult to define which stage of the viral lifecycle is affected by a given adaptive mutation.
NIH researchers have now developed a single-cycle virus production system that allows the stage of the viral lifecycle affected by a specific adaptive mutation to be determined. They have isolated a unique subclone of Huh 7 Hepatoma cells, S29, that permits HCV replication and infectious virion release, but is resistant to infection by HCV. This permits the use of single cycle growth studies, and removes the confounding effects of virus re-infection allowing progress to be made on structure/function studies, or on studies of the effects of drugs on replication and virus assembly.
- HCV drug discovery
- HCV single-cycle virus studies
- HCV structure/function studies