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J. Virol. doi:10.1128/JVI.02053-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Cellular determinants of hepatitis C virus assembly, maturation, degradation and secretion

Division of Experimental Pathology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA92037 U.S.A. and Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA 92093, USA

^* To whom correspondence should be addressed. Email: fchisari{at}scripps.edu.

	Abstract

Intracellular infectious hepatitis C virus (HCV) particles display distinctly higher buoyant density than secreted virus particles, suggesting that the characteristic low-density of extracellular HCV particles is acquired during viral egress. We took advantage of this difference to examine the determinants of assembly, maturation, degradation and egress of infectious HCV particles. The results demonstrate that HCV assembly and maturation occur in the endoplasmic reticulum (ER) and post-ER compartments, respectively, and that both depend on microsomal transfer protein (MTP) and apolipoprotein B (apoB) in a manner that parallels the formation of very low density lipoproteins (VLDL). In addition, they illustrate that only low-density particles are efficiently secreted and that immature particles are actively degraded in a proteasome-independent manner in a post- ER compartment of the cell. These results suggest that, by co-opting the VLDL assembly, maturation, degradation and secretory machinery of the cell, HCV acquires its hepatocyte tropism and, by mimicry, its tendency to persist.

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