Hepatitis C virus quasispecies in cancerous and noncancerous hepatic lesions: the core protein-encoding region.
We have shown that highly proofreading DNA polymerase is required for the polymerase chain reaction in the genetic analysis of hepatitis C virus (HCV). To clarify the status of HCV quasispecies in hepatic tissue using proofreading DNA polymerase, we performed a genetic analysis of the HCV core protein-encoding region in cancerous and noncancerous lesions derived from 4 patients with hepatocellular carcinoma. In contrast to the previously published data, we observed neither deletions nor stop codons in the analyzed region and no significant difference in the complexity of HCV quasispecies between cancerous and noncancerous lesions. This result suggests that the HCV core gene is never structurally defective in hepatic tissues, including cancerous lesions. However, in 3 of the patients, the consensus HCV species differed between cancerous and noncancerous lesions, suggesting that the predominant replicating HCV species differs between these 2 types of lesions. Moreover, during the course of the study, we obtained several interesting variants possessing a substitution at codon 9 of the core gene, whose substitution has been shown to induce the production of the F protein synthesized by a - 2/+1 ribosomal frameshift.
Alam
Shahjalal S
SS
Department of Molecular Biology, Okayama University Graduate School of Medicine and Dentistry, Japan.
Nakamura
Takashi
T
Naganuma
Atsushi
A
Nozaki
Akito
A
Nouso
Kazuhiro
K
Shimomura
Hiroyuki
H
Kato
Nobuyuki
N
D000368:Aged; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D016384:Consensus Sequence; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D005260:Female; D015967:Gene Expression Regulation, Viral; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D013045:Species Specificity; D014758:Viral Core Proteins / Q000235:genetics*
D012367:RNA, Viral; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D004259:DNA-Directed DNA Polymerase