Inhibition of interferon-inducible MxA protein expression by hepatitis B virus capsid protein.
Chronic hepatitis B treatment has been significantly improved by interferon (IFN) treatment. However, some studies have suggested that hepatitis B virus (HBV) might have a direct effect on the resistance to IFN. Defective particles, generated by spliced HBV RNA and associated with chronic hepatitis B, have been previously characterized; expression of these particles leads to cytoplasmic accumulation of the capsid protein. The aim of this study was to investigate the role of these defective genomes in IFN resistance. The global antiviral activity of IFN was studied by virus yield reduction assays, the expression of three IFN-induced antiviral proteins was analysed by Western blotting and confocal microscopy, and the regulation of MxA gene expression was studied by Northern blotting and the luciferase assay, in Huh7 cells transfected with a complete or the defective HBV genome. Results showed that the expression of the defective genome reduces the antiviral activity of IFN and that this modulation involves a selective inhibition of MxA protein induction by the HBV capsid protein. Our results also show the trans-suppressive effect of the HBV capsid on the MxA promoter, which might participate in this phenomenon. In conclusion, this study shows a direct interplay between the IFN-sensitive pathway and the capsid protein and might implicate this defective HBV genome in virus persistence.
Rosmorduc
O
O
Sirma
H
H
Soussan
P
P
Gordien
E
E
Lebon
P
P
Horisberger
M
M
Br Chot
C
C
Kremsdorf
D
D
D015152:Blotting, Northern; D015153:Blotting, Western; D002213:Capsid / Q000235:genetics / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D007372:Interferons / Q000378:metabolism / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D009154:Mutation; D064547:Myxovirus Resistance Proteins; D010957:Plasmids / Q000235:genetics; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D064547:Myxovirus Resistance Proteins; D011506:Proteins; D007372:Interferons; D008156:Luciferases; D019204:GTP-Binding Proteins