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      Comparison of the Mechanisms of Drug Resistance among HIV, Hepatitis B, and Hepatitis C

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          Abstract

          Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) are the most prevalent deadly chronic viral diseases. HIV is treated by small molecule inhibitors. HBV is treated by immunomodulation and small molecule inhibitors. HCV is currently treated primarily by immunomodulation but many small molecules are in clinical development. Although HIV is a retrovirus, HBV is a double-stranded DNA virus, and HCV is a single-stranded RNA virus, antiviral drug resistance complicates the development of drugs and the successful treatment of each of these viruses. Although their replication cycles, therapeutic targets, and evolutionary mechanisms are different, the fundamental approaches to identifying and characterizing HIV, HBV, and HCV drug resistance are similar. This review describes the evolution of HIV, HBV, and HCV within individuals and populations and the genetic mechanisms associated with drug resistance to each of the antiviral drug classes used for their treatment.

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          Most cited references279

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          Diagnosis, management, and treatment of hepatitis C: an update.

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            Robust hepatitis C virus infection in vitro.

            The absence of a robust cell culture model of hepatitis C virus (HCV) infection has severely limited analysis of the HCV life cycle and the development of effective antivirals and vaccines. Here we report the establishment of a simple yet robust HCV cell culture infection system based on the HCV JFH-1 molecular clone and Huh-7-derived cell lines that allows the production of virus that can be efficiently propagated in tissue culture. This system provides a powerful tool for the analysis of host-virus interactions that should facilitate the discovery of antiviral drugs and vaccines for this important human pathogen.
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              Rates of spontaneous mutation.

              Rates of spontaneous mutation per genome as measured in the laboratory are remarkably similar within broad groups of organisms but differ strikingly among groups. Mutation rates in RNA viruses, whose genomes contain ca. 10(4) bases, are roughly 1 per genome per replication for lytic viruses and roughly 0.1 per genome per replication for retroviruses and a retrotransposon. Mutation rates in microbes with DNA-based chromosomes are close to 1/300 per genome per replication; in this group, therefore, rates per base pair vary inversely and hugely as genome sizes vary from 6 x 10(3) to 4 x 10(7) bases or base pairs. Mutation rates in higher eukaryotes are roughly 0.1-100 per genome per sexual generation but are currently indistinguishable from 1/300 per cell division per effective genome (which excludes the fraction of the genome in which most mutations are neutral). It is now possible to specify some of the evolutionary forces that shape these diverse mutation rates.
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                Author and article information

                Journal
                Viruses
                Viruses
                Molecular Diversity Preservation International (MDPI)
                1999-4915
                December 2010
                14 December 2010
                : 2
                : 12
                : 2696-2739
                Affiliations
                Departments of Medicine and Pathology, Stanford University, Stanford, CA 94305, USA; E-Mails: severine@ 123456stanford.edu (S.M.T.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: rshafer@ 123456stanford.edu ; Tel.: +1-650-725-2946; Fax: +1-650-725-2088.
                Article
                viruses-02-02696
                10.3390/v2122696
                3020796
                21243082
                3adae63d-b08b-4c51-a280-92570f932628
                © 2010 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 24 October 2010
                : 15 November 2010
                : 7 December 2010
                Categories
                Review

                Microbiology & Virology
                hiv,drug resistance,hcv,antiviral therapy,evolution,quasispecies,hbv
                Microbiology & Virology
                hiv, drug resistance, hcv, antiviral therapy, evolution, quasispecies, hbv

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