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Persistent hepatitis C virus infection in vitro: coevolution of virus and host.

Zhong, Jin and Gastaminza, Pablo and Chung, Josan and Stamataki, Zania and Isogawa, Masanori and Cheng, Guofeng and McKeating, Jane A and Chisari, Francis V (2006) Persistent hepatitis C virus infection in vitro: coevolution of virus and host. Journal of virology, 80 (22). pp. 11082-93. ISSN 0022-538X

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The virological and cellular consequences of persistent hepatitis C virus (HCV) infection have been elusive due to the absence of the requisite experimental systems. Here, we report the establishment and the characteristics of persistent in vitro infection of human hepatoma-derived cells by a recently described HCV genotype 2a infectious molecular clone. Persistent in vitro infection was characterized by the selection of viral variants that displayed accelerated expansion kinetics, higher peak titers, and increased buoyant densities. Sequencing analysis revealed the selection of a single adaptive mutation in the HCV E2 envelope protein that was largely responsible for the variant phenotype. In parallel, as the virus became more aggressive, cells that were resistant to infection emerged, displaying escape mechanisms operative at the level of viral entry, HCV RNA replication, or both. Collectively, these results reveal the existence of coevolutionary events during persistent HCV infection that favor survival of both virus and host.

Type of Work:Article
Date:2006 (Publication)
School/Faculty:Schools (1998 to 2008) > School of Medicine
Department:Immunity and Infection
Subjects:R Medicine (General)
QR355 Virology
QR180 Immunology
QR Microbiology
Institution:University of Birmingham
Copyright Holders:American Society for Microbiology.
ID Code:488
Refereed:YES
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