Expression of hepatitis C virus proteins in epithelial intestinal cells in vivo.
Previous work on hepatitis C virus (HCV) led to the discovery of a new form of virus particle associating virus and lipoprotein elements. These hybrid particles (LVP for lipo-viro-particles) are enriched in triglycerides and contain at least apolipoprotein B (apoB), HCV RNA and core protein. These findings suggest that LVP synthesis could occur in liver and intestine, the two main organs specialized in the production of apoB-containing lipoprotein. To identify the site of LVP production, the genetic diversity and phylogenetic relationship of HCV quasispecies from purified LVP, whole serum and liver biopsies from chronically infected patients were studied. HCV quasispecies from LVP and liver differed significantly, suggesting that LVP were not predominantly synthesized in the liver but might also originate in the intestine. The authors therefore searched for the presence of HCV in the small intestine. Paraffin-embedded intestinal biopsies from 10 chronically HCV-infected patients and from 12 HCV RNA-negative controls (10 anti-HCV antibody-negative and two anti-HCV antibody-positive patients) were tested for HCV protein expression. HCV NS3 and NS5A proteins were stained in small intestine epithelial cells in four of the 10 chronically infected patients, and not in controls. Cells expressing HCV proteins were apoB-producing enterocytes but not mucus-secreting cells. These data indicate that the small intestine can be infected by HCV, and identify this organ as a potential reservoir and replication site. This further emphasizes the interaction between lipoprotein metabolism and HCV, and offers new insights into hepatitis C infection and pathophysiology.
Deforges
Séverine
S
INSERM U503, IFR128 Biosciences Lyon Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
Evlashev
Alexey
A
INSERM U503, IFR128 Biosciences Lyon Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
Perret
Magali
M
INSERM U503, IFR128 Biosciences Lyon Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
Sodoyer
Mireille
M
UMR 2142 CNRS-bioMérieux, IFR128 Biosciences Lyon Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
Pouzol
Stéphane
S
UMR 2142 CNRS-bioMérieux, IFR128 Biosciences Lyon Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
Scoazec
Jean-Yves
JY
Laboratoire d'Anatomo-Pathologie, Hôpital E. Herriot, 5 place Arsonval, 69003 Lyon, France.
Bonnaud
Bertrand
B
UMR 2142 CNRS-bioMérieux, IFR128 Biosciences Lyon Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
Diaz
Olivier
O
INSERM U503, IFR128 Biosciences Lyon Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
Paranhos-Baccalà
Glaucia
G
UMR 2142 CNRS-bioMérieux, IFR128 Biosciences Lyon Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
Lotteau
Vincent
V
INSERM U503, IFR128 Biosciences Lyon Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
André
Patrice
P
INSERM U503, IFR128 Biosciences Lyon Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
D000328:Adult; D001055:Apolipoproteins B / Q000378:metabolism; D001706:Biopsy; D004847:Epithelial Cells / Q000821:virology; D014644:Genetic Variation; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000473:pathology / Q000821:virology*; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008565:Membrane Proteins / Q000097:blood; D008969:Molecular Sequence Data; D010802:Phylogeny; D014759:Viral Envelope Proteins / Q000032:analysis / Q000235:genetics; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000032:analysis / Q000378:metabolism*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D001055:Apolipoproteins B; D008565:Membrane Proteins; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C087035:E1 protein, Hepatitis C virus; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C091015:glycoprotein E2, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase