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

P Gastaminza, G Cheng, S Wieland, J Zhong… - Journal of …, 2008 - Am Soc Microbiol
P Gastaminza, G Cheng, S Wieland, J Zhong, W Liao, FV Chisari
Journal of virology, 2008Am Soc Microbiol
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 …
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.
American Society for Microbiology