Abstract
BackgroundHepatitis C virus (HCV) infection afflicts about 170 million individuals worldwide. However, the HCV life cycle is only partially understood because it has not been possible to infect normal human hepatocytes in culture. The current Huh-7 systems use cloned, synthetic HCV RNA expressed in hepatocellular carcinoma cells to produce virions, but these cells cannot be infected with naturally occurring HCV obtained from infected patients.Methodology/Principal FindingsHere, we describe a human hepatocyte culture permissible to the direct infection with naturally occurring HCV genotypes 1, 2, 3 and 4 in the blood of HCV-infected patients. The culture system mimics the biology and kinetics of HCV infection in humans, and produces infectious virions that can infect naïve human hepatocytes.Conclusions/SignificanceThis culture system should complement the existing systems, and may facilitate the understanding of the HCV life cycle, its effects in the natural host cell, the hepatocyte, as well as the development of novel therapeutics and vaccines.
Highlights
An estimated 170 million individuals have chronic hepatitis C virus (HCV) infection worldwide [1]
Some stringent conditions of the culture system were required for achieving a successful Hepatitis C virus (HCV) infection of human hepatocytes
HCV infection was achieved in human hepatocyte cultures from 29 different liver donors
Summary
An estimated 170 million individuals have chronic hepatitis C virus (HCV) infection worldwide [1]. The current Huh-7-derived HCV virions system uses nonnaturally occurring, cloned HCV genotype 2a strain (JFH-1) [7], cloned HCV genotype 1a ( H77-S) containing five adaptive mutations [10] , or cloned HCV genotype 1b [11] Limitations of this method are the use of cloned HCV, and the failure to infect these cells with naturally occurring HCV obtained from infected patients [14]. We report the development of a normal human hepatocyte culture system permissible to the infection with, and physiologically significant amplification of, naturally occurring HCV
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