TY - JOUR
T1 - Cell culture-adaptive NS3 mutations required for the robust replication of genome-length hepatitis C virus RNA
AU - Abe, Ken ichi
AU - Ikeda, Masanori
AU - Dansako, Hiromichi
AU - Naka, Kazuhito
AU - Kato, Nobuyuki
N1 - Funding Information:
We thank T. Nakamura and A. Morishita for their technical assistance. This work was supported by a grant-in-aid for the third-term comprehensive 10-year strategy for cancer control and by a grant-in-aid for research on hepatitis, both from the Ministry of Health, Labor, and Welfare of Japan. K.A. was supported by a Research Fellowship from the Japan Society for the Promotion of Science (JSPS) for Young Scientists.
PY - 2007/4
Y1 - 2007/4
N2 - We recently established a genome-length HCV RNA-replicating cell line (O strain of genotype 1b; here called O cells) using cured cells derived from sO cells, in which HCV subgenomic replicon RNA with an adaptive NS5A mutation (S2200R) is replicated. Characterization of the O cells revealed a second adaptive NS3 mutation (K1609E) required for genome-length HCV RNA replication. To clarify the role of adaptive mutation in genome-length HCV RNA replication, we newly established one and three kinds of genome-length HCV RNA-replicating cell lines possessing the cell background of sO and O cells, respectively, and found additional adaptive NS3 mutations (Q1112R, P1115L, and E1202G) required for the robust replication of genome-length HCV RNA. We further found that specific combinations of adaptive NS3 mutations drastically enhanced HCV RNA replication, regardless of the cell lines examined. These findings suggest that specific viral factors may affect the replication level of genome-length HCV RNA.
AB - We recently established a genome-length HCV RNA-replicating cell line (O strain of genotype 1b; here called O cells) using cured cells derived from sO cells, in which HCV subgenomic replicon RNA with an adaptive NS5A mutation (S2200R) is replicated. Characterization of the O cells revealed a second adaptive NS3 mutation (K1609E) required for genome-length HCV RNA replication. To clarify the role of adaptive mutation in genome-length HCV RNA replication, we newly established one and three kinds of genome-length HCV RNA-replicating cell lines possessing the cell background of sO and O cells, respectively, and found additional adaptive NS3 mutations (Q1112R, P1115L, and E1202G) required for the robust replication of genome-length HCV RNA. We further found that specific combinations of adaptive NS3 mutations drastically enhanced HCV RNA replication, regardless of the cell lines examined. These findings suggest that specific viral factors may affect the replication level of genome-length HCV RNA.
KW - Adaptive mutation
KW - Genome-length HCV RNA replication
KW - HCV RNA-replicating cell line
KW - Hepatitis C virus
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U2 - 10.1016/j.virusres.2006.12.011
DO - 10.1016/j.virusres.2006.12.011
M3 - Article
C2 - 17239465
AN - SCOPUS:33947136220
SN - 0168-1702
VL - 125
SP - 88
EP - 97
JO - Virus research
JF - Virus research
IS - 1
ER -
