Genomic Characterization and Mutation Rate of Hepatitis C Virus Isolated From a Patient Who Contracted Hepatitis During an Epidemic of non-A, non-B Hepatitis in Japan
To investigate the genomic characterization of hepatitis C virus (HCV) isolated from a patient who contracted hepatitis during an epidemic of non-A, non-B (NANB) hepatitis in Shimizu city, Japan, we have cloned the nucleotide sequence of the viral genome (HCV-KF) spanning the structural domain. When compared to other previously reported HCV isolates, HCV-KF showed an overall identity at the amino acid level of 90.0 to 92.1% with Japanese isolates and 80.9 to 82.1% with American-like isolates. The HCV-KF genome displays an insertion of three nucleotides in-frame (corresponding to one amino acid) found at the junction between the E1 and E2/NS1 region. The mutation rate of the HCV-KF genome was assessed by comparing the nucleotide and deduced amino acid sequences of the viral RNA obtained from the serum of the original patient with viral sequences derived from the serum of a chimpanzee inoculated with the same serum 9 years previously. The substitution rate of the viral genome was estimated at 0.9 × 10−13 nucleotides per site per year for the HCV structural region. The highest mutation rate was found in the hypervariable region within the E2/NS1 domain. It is suggested that the outbreak in Shimizu city was caused by a strain of HCV closely related to the Japanese-like subgroup of isolates.
AbeK.,
ShikataT.,
FujisawaK.,
YamauchiM.,
MatsushitaH.,
SuzukiH.,
OdaT.1986; Transmission of non-A, non-B hepatitis agent to chimpanzees from patients of epidemic hepatitis. Japanese Journal of Medical Science and Biology 39:119–127
ChooQ.-L.,
KuoG.,
WeinerA. J.,
OverbyL.,
BradleyD. W.,
HoughtonM.1989; Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244:359–362
ChooQ.-L.,
RichmanK. H.,
HanJ. H.,
BergerK.,
LeeC.,
DongC.,
GallegosC.,
CoitD.,
Medina-SelbyA.,
BarrP. J.,
WeinerA. J.,
BradleyD. W.,
KuoG.,
HoughtonM.1991; Genetic organization and diversity of the hepatitis C virus. Proceedings of the National Academy of Sciences, U.S.A. 88:2451–2455
EstebanJ. I.,
EstebanR.,
ViladomiuL.,
Lopez-TalaveraJ. C.,
GomalezA.,
HernandezJ. M.,
RogetM.,
VargasV.,
GenescaJ.,
ButiM.,
GuardiaJ.1989; Hepatitis C virus antibodies among risk groups in Spain. Lancet ii:294–296
FujisawaK.,
YamauchiM.,
KamedaH.,
ShikataT.,
NishiokaK.1990; Detection of antibodies to hepatitis C virus in patients involved in an outbreak of non-A, non-B hepatitis in the Okitsu area of Japan. In Viral Hepatitis and Liver Disease pp. 415–417 Edited by
HollingerF. B.,
LemonS. M.,
MargolisH.
New York: Williams and Wilkins Press;
HahnB. H.,
ShawG. M.,
TaylorM. E.,
RedfieldR. R.,
MarkhamP. D.,
SalahuddinS. Z.,
Wong-StaalF.,
GalloR. C.,
ParksE. S.,
ParksW. P.1986; Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS. Science 232:1548–1553
HoughtonM.,
WeinerA.,
HanJ.,
KuoG.,
ChooQ.-L.1991; Molecular biology of the hepatitis C viruses: implications for diagnosis, development and control of viral disease. Hepatology 14:381–388
InchauspeG.,
ZebedeeS.,
LeeD.-H.,
SugitaniM.,
NasoffM.,
PrinceA. M.1991; Genomic structure of the human prototype strain H of hepatitis C virus: comparison with American and Japanese isolates. Proceedings of the National Academy of Sciences, U.S.A. 88:10292–10296
KatoN.,
HijikataM.,
OotsuyamaY.,
NakagawaM.,
OhkoshiS.,
SugimuraT.,
ShimotohnoK.1990; Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proceedings of the National Academy of Sciences, U.S.A. 87:9524–9528
KiyosawaK.,
SodeyamaT.,
TanakaE.,
ShimizuS.,
FurutaS.,
MiyazakiY.,
AkahaneY.,
SuzukiH.1991; Intrafamilial transmission of hepatitis C virus in Japan. Journal of Medical Virology 33:114–116
KuoG.,
ChooQ.-L.,
AlterH. J.,
GitnickG. I.,
RedekerA. G.,
PurcellR. H.,
MiyamuraT.,
DienstagJ. L.,
AlterM. J.,
LeeW. S.,
KuoC.,
BergerK.,
ShusterJ. R.,
OverbyL. R.,
BradleyD. W.,
HoughtonM.1989; An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244:362–364
MillerR. H.,
PurcellR. H.1990; Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups. Proceedings of the National Academy of Sciences, U.S.A. 87:2057–2061
NasoffM. S.,
ZebedeeS. L.,
InchauspeG.,
PrinceA. M.1991; Identification of an immunodominant epitope within the capsid protein of hepatitis C virus. Proceedings of the National Academy of Sciences, U.S.A. 88:5462–5466
OgataN.,
AlterH. J.,
MillerR. H.,
PurcellR. H.1991; Nucleotide sequence and mutation rate of the H strain of hepatitis C virus. Proceedings of the National Academy of Sciences, U.S.A. 88:3392–3396
OkamotoH.,
MunekataE.,
TsudaF.,
TakahashiK.,
YotsumotoS.,
TanakaT.,
TachibanaK.,
AkahaneY.,
SugaiY.,
MiyakawaY.,
MayumiM.1990a; Enzyme-linked immunosorbent assay for antibodies against the capsid protein of hepatitis C virus with a synthetic oligopeptide. Japanese Journal of Experimental Medicine 60:223–233
OkamotoH.,
OkadaS.,
SugiyamaY.,
YotsumotoS.,
TanakaT.,
YoshizawaH.,
TsudaF.,
MiyakawaY.,
MayumiM.1990b; The 5’-terminal sequence of the hepatitis C virus genome. Japanese Journal of Experimental Medicine 60:167–177
SaagM. S.,
HahnB. H.,
GibbonsJ.,
LiY.,
ParksE. S.,
ParksW. P.,
ShawG. M.1988; Extensive variation of human immunodeficiency virus type 1 in vivo
. Nature, London 334:440–444
TakamizawaA.,
MoriC.,
FukeI.,
ManabeS.,
MurakamiS.,
FujitaJ.,
OnishiE.,
AndohT.,
YoshidaI.,
OkayamaH.1991; Structure and organization of the hepatitis C virus genome isolated from human carriers. Journal of Virology 65:1105–1113
TakeuchiK.,
KuboY.,
BoonmarS.,
WatanabeY.,
KatayamaT.,
ChooQ.-L.,
KuoG.,
HoughtonM.,
SaitoI.,
MiyamuraT.1990; The putative nucleocapsid and envelope protein genes of hepatitis C virus determined by comparison of the nucleotide sequences of two isolates derived from an experimentally infected chimpanzee and healthy human carriers. Journal of General Virology 71:3027–3033
WeinerA. J.,
BrauerM. J.,
RosenblattJ.,
RichmanK. H.,
TungJ.,
CrawfordK.,
BoninoF.,
SaraccoG.,
ChooQ.-L.,
HoughtonM.,
HanJ. H.1991; Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. Virology 180:842–848
YamauchiM.,
NakajimaH.,
KimuraK.,
FujisawaK.,
KamedaH.,
NakaharaM.,
SatohY.,
KawamuraH.1983; An epidemic of non-A, non-B hepatitis in Japan. American Journal of Gastroenterology 78:652–655
Genomic Characterization and Mutation Rate of Hepatitis C Virus Isolated From a Patient Who Contracted Hepatitis During an Epidemic of non-A, non-B Hepatitis in Japan