Effect of mutation in the hepatitis C virus nonstructural 5B region on HCV replication.
BACKGROUND
We have reported that the presence of a mutation at the hepatitis C virus (HCV) nonstructural protein 5B (NS5B), defined as a change in amino acids at sites specific for a different reported genotype, was related to complete response (CR) to interferon (IFN) therapy in patients with chronic hepatitis C (CHC) with genotype 1b. The present study assessed the impact of the NS5B mutation on the replication of HCV in these patients.


METHODS
Genotype-specific mutations of HCV NS5B were determined by direct sequencing. We measured HCV-RNA titers in serum by real-time detected polymerase chain reaction (PCR), and serum HCV core protein levels (as a marker of HCV-RNA replication) were measured using an enzyme immunoassay in patients with CHC genotype 1b. RNA-dependent RNA polymerase (RdRp) activity was measured by Behrens' method in liver cirrhosis patients infected with HCV (n = 13) and in those infected with hepatitis B virus (HBV; n = 2).


RESULTS
The titers of HCV-RNA (n = 44) and the levels of HCV core protein (n = 41) were significantly lower in patients with the HCV genotype 1b mutant compared with wild-type HCV (P < 0.05). RdRp activity in liver tissue did not show any correlation with the HCV NS5B mutation.


CONCLUSIONS
HCV NS5B genotype-specific mutations in HCV genotype 1b may influence HCV replication.
Okura
Izumi
I
The Third Department of Internal Medicine, Ehime University School of Medicine, Ehime 791-0295, Japan.
Horiike
Norio
N
Michitaka
Kojiro
K
Onji
Morikazu
M
D004252:DNA Mutational Analysis; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D014542:Uridine Monophosphate / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
D012367:RNA, Viral; D014542:Uridine Monophosphate; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase