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J. Virol. doi:10.1128/JVI.00640-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A dynamic view of hepatitis C virus replication complexes

Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, NY 10021; Department of Medicine II, University of Freiburg, D-79106 Freiburg, Germany; Department of Virology, Hannover Medical School, D-30625 Hannover, Germany; and Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, CH-1011 Lausanne, Switzerland

^* To whom correspondence should be addressed. Email: Darius.Moradpour{at}chuv.ch. ricec{at}rockefeller.edu.

	Abstract

Hepatitis C virus (HCV) replicates its genome in a membrane-associated replication complex (RC). Specific membrane alterations, designated membranous webs, represent predominant sites of HCV RNA replication. The principles governing HCV RC and membranous web formation are poorly understood. Here, we used replicons harboring a green fluorescent protein (GFP) insertion in nonstructural protein 5A (NS5A) to study HCV RCs in live cells. Two distinct patterns of NS5A-GFP were observed: Large structures, representing membranous webs, showed restricted motility, were stable over many hours, were partitioned among daughter cells during cell division, and displayed a static internal architecture without detectable exchange of NS5A-GFP. By contrast, small structures, presumably representing small RCs, showed fast, saltatory movements over long distances. Both populations were associated with endoplasmic reticulum (ER) tubules but only small RCs showed ER-independent, microtubule (MT)-dependent transport. We suggests that this MT-dependent transport sustains two distinct RC populations which are both required during the HCV life cycle.