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Expression of hepatitis C virus proteins in epithelial intestinal cells in vivo

Séverine Deforges^1,

Alexey Evlashev^1,

¹ INSERM U503, IFR128 Biosciences Lyon Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France
² UMR 2142 CNRS-bioMérieux, IFR128 Biosciences Lyon Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France
³ Laboratoire d'Anatomo-Pathologie, Hôpital E. Herriot, 5 place Arsonval, 69003 Lyon, France

Correspondence
Patrice André
andre{at}cervi-lyon.inserm.fr

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.

The GenBank/EMBL/DDBJ accession numbers of the sequences described in this article are AY600628–AY600858.

A figure showing how mAb 4F3H2 stains NS5A-expressing cells is available from JGV Online.

These authors contributed equally to this work.

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