TY - JOUR
T1 - Marked sequence diversity in the putative envelope proteins of hepatitis C viruses
AU - Kato, Nobuyuki
AU - Ootsuyama, Yuko
AU - Tanaka, Torahiko
AU - Nakagawa, Masanori
AU - Nakazawa, Takahide
AU - Muraiso, Kanae
AU - Ohkoshi, Showgo
AU - Hijikata, Makoto
AU - Shimotohno, Kunitada
N1 - Funding Information:
We are grateful to Dr. Y. Kobayashi for helpful suggestionsT. his work was supportedb y a Grant-in-Aid for Cancer Researchf rom the Ministry of Health and Welfare, and a Grant-in-Aid from the Ministry of Health and Welfare for a Comprehensivel o-Year Strategyo f Cancer Control, Japan. K.M. and T.N. are recipientso f Research Resident Fellowshipsf rom the Foundation for Promotion of Cancer Research.W e thank memberso f the National Cancer Center Hospital for surgicals pecimenso f livers.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1992/2
Y1 - 1992/2
N2 - The nucleotide sequences of cDNAs (414 base pairs) encoding parts of putative envelope proteins (gp35 and gp70) of 40 isolates of hepatitis C virus (HCV-J) derived from 30 independent plasma or liver specimens from Japanese patients (13 with chronic hepatitis, 14 with hepatocellular carcinoma and 3 hemophiliacs who had received imported clotting factors), were analyzed using the polymerase chain reaction. Approximately 29-38% of the nucleotide sequences of the HCV-J isolates examined differed from those of isolates from the United States (HCV-US). Furthermore, 12-24% and 8-17% sequence diversities were found within the isolates of HCV-J and HCV-US, respectively. The diversities of the amino acid sequences were the same or greater than those of the nucleotide sequences. We confirmed that two hypervariable regions (HVR1 and HVR2) were present in this amplified region, as described in our previous report (Hijikata et al., 1991a) and we found that the HVR1 regions of HCV-J and HCV-US were 27 and 21 amino acids in length, respectively, and began from the N-terminal amino acid of gp70. HVR2 was found in HCV-J, but not in HCV-US isolates, in which the corresponding region of the genome was conserved. During the analysis, plural HCV genomes were found in 6 of 30 specimens. These plural HCV genomes in a single specimen were concluded to be derived from the same HCV ancestor, because of their relative low sequence diversities (about 10% in their nucleotide sequences). We also obtained evidence for the first time that RNA recombination occurred between plural HCV genomes in a single patient. These results suggest that the mutation rate in the envelope region of the HCV genome is quite high and that the genetic heterogeneity of this region may be involved in persistent HCV infection.
AB - The nucleotide sequences of cDNAs (414 base pairs) encoding parts of putative envelope proteins (gp35 and gp70) of 40 isolates of hepatitis C virus (HCV-J) derived from 30 independent plasma or liver specimens from Japanese patients (13 with chronic hepatitis, 14 with hepatocellular carcinoma and 3 hemophiliacs who had received imported clotting factors), were analyzed using the polymerase chain reaction. Approximately 29-38% of the nucleotide sequences of the HCV-J isolates examined differed from those of isolates from the United States (HCV-US). Furthermore, 12-24% and 8-17% sequence diversities were found within the isolates of HCV-J and HCV-US, respectively. The diversities of the amino acid sequences were the same or greater than those of the nucleotide sequences. We confirmed that two hypervariable regions (HVR1 and HVR2) were present in this amplified region, as described in our previous report (Hijikata et al., 1991a) and we found that the HVR1 regions of HCV-J and HCV-US were 27 and 21 amino acids in length, respectively, and began from the N-terminal amino acid of gp70. HVR2 was found in HCV-J, but not in HCV-US isolates, in which the corresponding region of the genome was conserved. During the analysis, plural HCV genomes were found in 6 of 30 specimens. These plural HCV genomes in a single specimen were concluded to be derived from the same HCV ancestor, because of their relative low sequence diversities (about 10% in their nucleotide sequences). We also obtained evidence for the first time that RNA recombination occurred between plural HCV genomes in a single patient. These results suggest that the mutation rate in the envelope region of the HCV genome is quite high and that the genetic heterogeneity of this region may be involved in persistent HCV infection.
KW - Hepatocellular carcinoma
KW - Hypervariable region
KW - Non-A, non-B hepatitis
KW - Nucleotide sequence
KW - Polymerase chain reaction
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U2 - 10.1016/0168-1702(92)90038-B
DO - 10.1016/0168-1702(92)90038-B
M3 - Article
C2 - 1314471
AN - SCOPUS:0026335327
VL - 22
SP - 107
EP - 123
JO - Virus Research
JF - Virus Research
SN - 0168-1702
IS - 2
ER -