TY - JOUR
T1 - An infectious molecular clone of a Japanese genotype 1b hepatitis C virus
AU - Beard, Michael R.
AU - Abell, Geoffrey
AU - Honda, Masao
AU - Carroll, Anthony
AU - Gartland, Margaret
AU - Clarke, Berwyn
AU - Suzuki, Koyu
AU - Lanford, Robert
AU - Sangar, David V.
AU - Lemon, Stanley M.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - We describe an infectious molecular clone of a Japanese genotype lb strain of hepatitis C virus (HCV-N). The molecularly cloned sequence of HCV- N was compared with alignments of other HCV sequences, leading to the identification of 15 unique, nonconservative amino acid substitutions within the HCV-N open reading frame (ORF). These were repaired to the consensus genotype lb residue, and the infectivity of RNA transcribed from the repaired clone was assessed by intrahepatic inoculation of a chimpanzee. Viral RNA was first detected in the serum of this chimpanzee 3 weeks following inoculation, and was intermittently present over the next 14 weeks. A strong and persistent anti-HCV serological response developed 13 weeks following inoculation, with seroconversion in the recombinant immunoblot assay (RIBA). A weaker, transient serological response, characterized by seroconversion in a third-generation enzyme-linked immunosorbent assay (ELISA) but not RIBA, occurred between weeks 1 and 5. This may have represented an anamnestic response to HCV antigens translated directly from the intrahepatically inoculated RNA, because the animal previously had undergone 2 unsuccessful attempts at rescue of HCV by intrahepatic RNA inoculation. There was neither biochemical nor histological evidence of liver disease. Although this is within the range of expected outcomes in an HCV-naive chimpanzee, prior immunologic priming may have modified the infection in this animal. The HCV- N clone is the first infectious molecular clone of HCV that is comprised entirely of genotype lb sequence, and it contains an ORF sequence that is significantly divergent from that of a previously described genotype la/lb chimera.
AB - We describe an infectious molecular clone of a Japanese genotype lb strain of hepatitis C virus (HCV-N). The molecularly cloned sequence of HCV- N was compared with alignments of other HCV sequences, leading to the identification of 15 unique, nonconservative amino acid substitutions within the HCV-N open reading frame (ORF). These were repaired to the consensus genotype lb residue, and the infectivity of RNA transcribed from the repaired clone was assessed by intrahepatic inoculation of a chimpanzee. Viral RNA was first detected in the serum of this chimpanzee 3 weeks following inoculation, and was intermittently present over the next 14 weeks. A strong and persistent anti-HCV serological response developed 13 weeks following inoculation, with seroconversion in the recombinant immunoblot assay (RIBA). A weaker, transient serological response, characterized by seroconversion in a third-generation enzyme-linked immunosorbent assay (ELISA) but not RIBA, occurred between weeks 1 and 5. This may have represented an anamnestic response to HCV antigens translated directly from the intrahepatically inoculated RNA, because the animal previously had undergone 2 unsuccessful attempts at rescue of HCV by intrahepatic RNA inoculation. There was neither biochemical nor histological evidence of liver disease. Although this is within the range of expected outcomes in an HCV-naive chimpanzee, prior immunologic priming may have modified the infection in this animal. The HCV- N clone is the first infectious molecular clone of HCV that is comprised entirely of genotype lb sequence, and it contains an ORF sequence that is significantly divergent from that of a previously described genotype la/lb chimera.
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U2 - 10.1002/hep.510300137
DO - 10.1002/hep.510300137
M3 - Article
C2 - 10385673
AN - SCOPUS:0033063225
VL - 30
SP - 316
EP - 324
JO - Hepatology
JF - Hepatology
SN - 0270-9139
IS - 1
ER -