Real-time imaging of hepatitis C virus infection using a fluorescent cell-based reporter system.

Hepatitis C virus (HCV), which infects 2-3% of the world population, is a causative agent of chronic hepatitis and the leading indication for liver transplantation. The ability to propagate HCV in cell culture (HCVcc) is a relatively recent breakthrough and a key tool in the quest for specific antiviral therapeutics. Monitoring HCV infection in culture generally involves bulk population assays, use of genetically modified viruses and/or terminal processing of potentially precious samples. Here we develop a cell-based fluorescent reporter system that allows sensitive distinction of individual HCV-infected cells in live or fixed samples. We demonstrate use of this technology for several previously intractable applications, including live-cell imaging of viral propagation and host response, as well as visualizing infection of primary hepatocyte cultures. Integration of this reporter with modern image-based analysis methods could open new doors for HCV research.

Predicting response to hepatitis C therapy.

Current treatment for chronic hepatitis C is expensive, is often accompanied by burdensome side effects, and, sadly, fails in almost half of cases. The ability to predict such failures prior to treatment could save a great deal of pain and expense for the patient with HCV. In this issue of the JCI, Aurora and colleagues describe the development of genetic markers predictive of treatment response based on a study of viral sequence variation (see the related article beginning on page 225). Genome-wide covariation analyses of pretreatment virus sequences from 94 patients showed distinct patterns of mutations strongly associated with the ultimate success or failure of treatment. Such analyses suggest markers predictive of response to therapy and may lead to new insights into the underlying biology of hepatitis C.