Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity.
It is well documented that a variety of viral quasispecies are found in the patients with chronic infection of hepatitis C virus (HCV). However, the significance of quasispecies in the specific infectivity to individual cell types remains unknown. In the present study, we analyzed the role of quasispecies of the genotype 2a clone, JFH1 (HCVcc), in specific infectivity to the hepatic cell lines, Huh7.5.1 and Hep3B. HCV RNA was electroporated into Huh7.5.1 cells and Hep3B/miR-122 cells expressing miR-122 at a high level. Then, we adapted the viruses to Huh7 and Hep3B/miR-122 cells by serial passages and termed the resulting viruses HCVcc/Huh7 and HCVcc/Hep3B, respectively. Interestingly, a higher viral load was obtained in the homologous combination of HCVcc/Huh7 in Huh7.5.1 cells or HCVcc/Hep3B in Hep3B/miR-122 cells compared with the heterologous combination. By using a reverse genetics system and deep sequence analysis, we identified several adaptive mutations involved in the high affinity for each cell line, suggesting that quasispecies of HCV participate in cell-specific infectivity.
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Takasuke
T
Fukuhara
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.|Laboratory of Veterinary Microbiology, School of Veterinary Medicine, Kitasato University, Aomori, Japan.
Satomi
S
Yamamoto
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Chikako
C
Ono
Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Shota
S
Nakamura
Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Daisuke
D
Motooka
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Hiroyuki
H
Mori
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Takeshi
T
Kurihara
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Asuka
A
Sato
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Tomokazu
T
Tamura
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.|Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Takashi
T
Motomura
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Toru
T
Okamoto
Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical &Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Michio
M
Imamura
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Toru
T
Ikegami
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Tomoharu
T
Yoshizumi
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yuji
Y
Soejima
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yoshihiko
Y
Maehara
Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical &Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Kazuaki
K
Chayama
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Yoshiharu
Y
Matsuura
D045744:Cell Line, Tumor; D005838:Genotype; D057809:HEK293 Cells; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity*; D022781:Hepatocytes / Q000821:virology; D058507:Host Specificity / Q000235:genetics*; D006801:Humans; D009154:Mutation; D014774:Virulence / Q000235:genetics