Suppression of hepatitis B virus enhancer 1 and 2 by hepatitis C virus core protein.
OBJECTIVE
Epidemiological studies have shown that coinfection or superinfection with hepatitis B virus (HBV) and C virus (HCV) frequently leads to the suppression of hepatitis B virus replication. The mechanism of this phenomenon is still unclear. Shih et al. [J Virol 1993;67:5823] reported a direct suppression of HBV replication by the core protein of HCV. The target structure of HCV core protein in this system remained unclear.


METHODS
As HCV core protein has been shown to influence expression from transcriptional elements, we studied whether HCV core protein altered the activity of the two HBV enhancers 1 and 2. Luciferase vectors for HBV enhancers 1 or 2 were cotransfected with expression constructs for HCV core protein in murine and human hepatocyte lines.


RESULTS
Full-length HCV core protein suppressed the HBV enhancer 1 up to 11-fold, the enhancer 2 3-4-fold. Suppression of HBV enhancer 1 by HCV core from genotype 1b was stronger than by HCV core of genotypes 3a or 1a. Carboxyterminally truncated core proteins had lower or no suppression activity.


CONCLUSIONS
These data suggest that HCV core protein may directly repress transcription of the HBV RNAs. This trans-repression may contribute to suppression of HBV replication in patients coinfected with both viruses.
Schüttler
Christian G
CG
Institut für Medizinische Virologie Justus-Liebig-Universität, Frankfurter Strasse 107, D-35392 Giessen, Germany.
Fiedler
Nicola
N
Schmidt
Katja
K
Repp
Reinald
R
Gerlich
Wolfram H
WH
Schaefer
Stephan
S
D000818:Animals; D002460:Cell Line; D004742:Enhancer Elements, Genetic / Q000187:drug effects*; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics* / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014758:Viral Core Proteins / Q000737:chemistry / Q000494:pharmacology*
D010446:Peptide Fragments; D014758:Viral Core Proteins