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

Academic Article
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Overview

authors

  • Gastaminza, P.
  • Cheng, G. F.
  • Wieland, Stefan
  • Zhong, J.
  • Liao, W.
  • Chisari, Francis

publication date

  • March 2008

journal

  • Journal of Virology  Journal

abstract

  • Intracellular infectious hepatitis C virus (HCV) particles display a distinctly higher buoyant density than do 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 and apolipoprotein B, 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 coopting the VLDL assembly, maturation, degradation, and secretory machinery of the cell, HCV acquires its hepatocyte tropism and, by mimicry, its tendency to persist.

subject areas

  • Apolipoproteins B
  • Base Sequence
  • Brefeldin A
  • Carrier Proteins
  • Cell Line
  • DNA Primers
  • Fluorescent Antibody Technique
  • Hepacivirus
  • RNA, Viral
  • Virus Assembly
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Identity

PubMed Central ID

  • PMC2258938

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.02053-07

PubMed ID

  • 18077707
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Additional Document Info

start page

  • 2120

end page

  • 2129

volume

  • 82

issue

  • 5

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