Effect of frameshift mutation in the pre-C region of hepatitis B virus on the X and C genes.
We have previously cloned a mutant hepatitis B virus (HBV) genome which had one thymidine addition in the pre-C region resulting in a frameshift mutation in the pre-C region and fusion of the X and C genes. We constructed plasmids containing serially deleted and/or back-mutated (authentic) pre-C regions to study the effect of the frameshift mutation. COS cells transfected with plasmids containing the frameshifted pre-C region produced a 21K C protein (P21c) but not a 22K partially processed pre-C protein (P22). On the other hand, COS cells transfected with plasmids containing the back-mutated pre-C region produced P22. This result was also observed in HepG2-K8 cells producing the mutant HBV particles. Therefore, the pre-C region of HBV is likely to be non-essential for virus replication. COS cells transfected with the plasmid containing a fused X-C open reading frame (ORF) produced a 40K X-C fusion protein. This X-C fusion protein exerted transcriptional trans-activation. These results suggest that the mutant HBV has a C gene with a defective pre-C region and a fused X-C ORF, and hence cannot synthesize 16K HBeAg (P16e).
Kim
S K
SK
Department of Molecular Biology, Seoul National University, Korea.
Jang
S K
SK
Rho
H M
HM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D016368:Frameshift Mutation / Q000235:genetics*; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D005814:Genes, Viral / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics*; D018936:Hepatitis C Antigens; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D014758:Viral Core Proteins / Q000032:analysis / Q000235:genetics*; D014760:Viral Fusion Proteins / Q000032:analysis / Q000235:genetics*
D006513:Hepatitis B e Antigens; D018936:Hepatitis C Antigens; D015534:Trans-Activators; D014758:Viral Core Proteins; D014760:Viral Fusion Proteins; C066051:X-C fusion protein, Hepatitis B virus; C499352:core protein p22, Hepatitis C virus; C069130:nucleocapsid protein, Hepatitis C virus