Efficient Initiation of HCV RNA Replication in Cell Culture

Author:

Blight Keril J.1,Kolykhalov Alexander A.1,Rice Charles M.12

Affiliation:

1. Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110–1093, USA.

2. Center for the Study of Hepatitis C, Rockefeller University, Box 64, 1230 York Avenue, New York, NY 10021, USA.

Abstract

Hepatitis C virus (HCV) infection is a global health problem affecting an estimated 170 million individuals worldwide. We report the identification of multiple independent adaptive mutations that cluster in the HCV nonstructural protein NS5A and confer increased replicative ability in vitro. Among these adaptive mutations were a single amino acid substitution that allowed HCV RNA replication in 10% of transfected hepatoma cells and a deletion of 47 amino acids encompassing the interferon (IFN) sensitivity determining region (ISDR). Independent of the ISDR, IFN-α rapidly inhibited HCV RNA replication in vitro. This work establishes a robust, cell-based system for genetic and functional analyses of HCV replication.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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