Scotomas in molecular virology and epidemiology of hepatitis C virus.

In the 1970s, scientists learned of a new pathogen causing non-A, non-B hepatitis. Classical approaches were used to isolate and characterize this new pathogen, but it could be transmitted experimentally only to chimpanzees and progress was slow until the pathogen was identified as hepatitis C virus (HCV) in 1989. Since then, research and treatment of HCV have expanded with the development of modern biological medicine: HCV genome organization and polyprotein processing were delineated in 1993; the first three-dimensional structure of HCV nonstructural protein (NS3 serine protease) was revealed in 1996; an infectious clone of HCV complementary DNA was first constructed in 1997; interferon and ribavirin combination therapy was established in 1998 and the therapeutic strategy gradually optimized; the HCV replicon system was produced in 1999; functional HCV pseudotyped viral particles were described in 2003; and recombinant infectious HCV in tissue culture was produced successfully in 2005. Recently, tremendous advances in HCV receptor discovery, understanding the HCV lifecycle, decryption of the HCV genome and proteins, as well as new anti-HCV compounds have been reported. Because HCV is difficult to isolate and culture, researchers have had to avail themselves to the best of modern biomedical technology; some of the major achievements in HCV research have not only advanced the understanding of HCV but also promoted knowledge of virology and cellular physiology. In this review, we summarize the advancements and remaining scotomas in the molecular virology and epidemiology of HCV.