Preferential association of Hepatitis C virus with apolipoprotein B48-containing lipoproteins.
Hepatitis C virus (HCV) in cell culture has a density comparable to that of other members of the family Flaviviridae, whereas in vivo infectious particles are found partially in low-density fractions, associated with triacylglycerol (TG)-rich lipoproteins (TRLs). In the blood of infected patients, HCV circulates as heterogeneous particles, among which are lipo-viroparticles (LVPs), globular particles rich in TG and containing viral capsid and RNA. The dual viral and lipoprotein nature of LVPs was addressed further with respect to apolipoprotein composition and post-prandial dynamic lipid changes. The TRLs exchangeable apoE, -CII and -CIII, but not the high-density lipoprotein apoA-II, were present on LVPs, as well as the viral envelope proteins. apoB100 and -B48, the two isoforms of the non-exchangeable apoB, were represented equally on LVPs, despite the fact that apoB48 was barely detectable in the plasma of these fasting patients. This indicates that a significant fraction of plasma HCV was associated with apoB48-containing LVPs. Furthermore, LVPs were enriched dramatically and rapidly in triglycerides after a fat meal. As apoB48 is synthesized exclusively by the intestine, these data highlight the preferential association of HCV with chylomicrons, the intestine-derived TRLs. These data raise the question of the contribution of the intestine to the viral load and suggest that the virus could take advantage of TRL assembly and secretion for its own production and of TRL fate to be delivered to the liver.
Diaz
Olivier
O
IFR 128 Biosciences Lyon Gerland, INSERM U503, 21 avenue Tony Garnier, 69007 Lyon, France.
Delers
François
F
Université Pierre et Marie Curie, INSERM, UMRS 505, Paris, France.
Maynard
Marianne
M
Service d'Hépato-Gastro-Entérologie, Hôtel Dieu, Hospices Civils de Lyon, France.
Demignot
Sylvie
S
Université Pierre et Marie Curie, INSERM, UMRS 505, Paris, France.
Zoulim
Fabien
F
Service d'Hépato-Gastro-Entérologie, Hôtel Dieu, Hospices Civils de Lyon, France.
Chambaz
Jean
J
Université Pierre et Marie Curie, INSERM, UMRS 505, Paris, France.
Trépo
Christian
C
Service d'Hépato-Gastro-Entérologie, Hôtel Dieu, Hospices Civils de Lyon, France.
Lotteau
Vincent
V
IFR 128 Biosciences Lyon Gerland, INSERM U503, 21 avenue Tony Garnier, 69007 Lyon, France.
André
Patrice
P
Laboratoire de Virologie, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, France.|IFR 128 Biosciences Lyon Gerland, INSERM U503, 21 avenue Tony Garnier, 69007 Lyon, France.
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000378:metabolism*; D004032:Diet; D016174:Hepacivirus / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000378:metabolism / Q000821:virology; D006801:Humans; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D012367:RNA, Viral