engleski

HUMAN LIVER CELLS CAN BE PROTECTED FROM HCV INFECTION BY CONTINUOUS INTRACELLULAR EXPRESSION OF HCV RNA ANALOGS

Hepatitis C virus infection frequently results chronic liver disease and liver failure. It is the most common indication for liver transplantation. The incidence of re-infection is virtually 100% for new livers transplanted into HCV (+) recipients. That infection results in a rapidly progressive liver damage which can result in failure of the graft. Currently, such infection and subsequent progressive liver disease cannot be prevented. We have shown that HCV RNA structural analogs can inhibit HCV RNA replication in infectious HCV systems. To determine whether human liver cells continuously expressing HCV structural analogs would be resistant to HCV infection. HCV RNA structural analogs were constructed and tested in a HCV genotype 1b BB7 replicon, and a Japanese fulminant hepatitis-1 (JFH-1) HCV genotype 2a infection model. An Huh7.5 cell line continuously expressing HCV structural analogs were prepared by stable transfection by a retroviral vector. The efficacy in preventing HCV replication in JFH-1 infection model was determined by real-time PCR quantification of HCV RNA. In stable transfected Huh7.5 cells with HCV structural analogs after exposure to JFH-1 HCV, cellular HCV RNA levels were significantly lower than in controls, indicating that the JFH-1 HCV genome replicated with lower efficiency in cells stable transfected with HCV structural analogs than in control cells. HCV infection is inhibited in human liver cells that continuously produce HCV structural analogs. If such cells were introduced into HCV-infected patients, these cells would be predicted to decrease HCV re-infection, and therefore, increase long-term success rates.

hepatitis C virus (HCV) infection; liver transplantation; graft failure; HCV RNA structural analogs; Japanese fulminant hepatitis-1 (JFH-1) HCV

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