Cellular determinants of hepatitis C virus assembly, maturation, degradation, and secretion.
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.
Gastaminza
Pablo
P
The Scripps Research Institute, Maildrop SBR-10, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Cheng
Guofeng
G
Wieland
Stefan
S
Zhong
Jin
J
Liao
Wei
W
Chisari
Francis V
FV
D001055:Apolipoproteins B / Q000502:physiology; D001483:Base Sequence; D020126:Brefeldin A / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology; D002460:Cell Line; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D019065:Virus Assembly / Q000502:physiology*
D001055:Apolipoproteins B; D002352:Carrier Proteins; D017931:DNA Primers; D012367:RNA, Viral; C106092:microsomal triglyceride transfer protein; D020126:Brefeldin A