Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity

Takasuke Fukuhara, Satomi Yamamoto, Chikako Ono, Shota Nakamura, Daisuke Motooka, Hiroyuki Mori, Takeshi Kurihara, Asuka Sato, Tomokazu Tamura, Takashi Motomura, Toru Okamoto, Michio Imamura, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Kazuaki Chayama, Yoshiharu Matsuura

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number45228
JournalScientific reports
Volume7
DOIs
Publication statusPublished - Mar 22 2017

Fingerprint

Hepacivirus
Viruses
Serial Passage
Reverse Genetics
Cell Line
Chronic Hepatitis C
Viral Load
Sequence Analysis
Hepatocytes
Clone Cells
Genotype
RNA
Mutation
Infection

All Science Journal Classification (ASJC) codes

  • General

Cite this

Fukuhara, T., Yamamoto, S., Ono, C., Nakamura, S., Motooka, D., Mori, H., ... Matsuura, Y. (2017). Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity. Scientific reports, 7, [45228]. https://doi.org/10.1038/srep45228

Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity. / Fukuhara, Takasuke; Yamamoto, Satomi; Ono, Chikako; Nakamura, Shota; Motooka, Daisuke; Mori, Hiroyuki; Kurihara, Takeshi; Sato, Asuka; Tamura, Tomokazu; Motomura, Takashi; Okamoto, Toru; Imamura, Michio; Ikegami, Toru; Yoshizumi, Tomoharu; Soejima, Yuji; Maehara, Yoshihiko; Chayama, Kazuaki; Matsuura, Yoshiharu.

In: Scientific reports, Vol. 7, 45228, 22.03.2017.

Research output: Contribution to journalArticle

Fukuhara, T, Yamamoto, S, Ono, C, Nakamura, S, Motooka, D, Mori, H, Kurihara, T, Sato, A, Tamura, T, Motomura, T, Okamoto, T, Imamura, M, Ikegami, T, Yoshizumi, T, Soejima, Y, Maehara, Y, Chayama, K & Matsuura, Y 2017, 'Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity', Scientific reports, vol. 7, 45228. https://doi.org/10.1038/srep45228
Fukuhara T, Yamamoto S, Ono C, Nakamura S, Motooka D, Mori H et al. Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity. Scientific reports. 2017 Mar 22;7. 45228. https://doi.org/10.1038/srep45228
Fukuhara, Takasuke ; Yamamoto, Satomi ; Ono, Chikako ; Nakamura, Shota ; Motooka, Daisuke ; Mori, Hiroyuki ; Kurihara, Takeshi ; Sato, Asuka ; Tamura, Tomokazu ; Motomura, Takashi ; Okamoto, Toru ; Imamura, Michio ; Ikegami, Toru ; Yoshizumi, Tomoharu ; Soejima, Yuji ; Maehara, Yoshihiko ; Chayama, Kazuaki ; Matsuura, Yoshiharu. / Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity. In: Scientific reports. 2017 ; Vol. 7.
@article{db69ababf93446538f38f6ca9eb0d351,
title = "Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity",
abstract = "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.",
author = "Takasuke Fukuhara and Satomi Yamamoto and Chikako Ono and Shota Nakamura and Daisuke Motooka and Hiroyuki Mori and Takeshi Kurihara and Asuka Sato and Tomokazu Tamura and Takashi Motomura and Toru Okamoto and Michio Imamura and Toru Ikegami and Tomoharu Yoshizumi and Yuji Soejima and Yoshihiko Maehara and Kazuaki Chayama and Yoshiharu Matsuura",
year = "2017",
month = "3",
day = "22",
doi = "10.1038/srep45228",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity

AU - Fukuhara, Takasuke

AU - Yamamoto, Satomi

AU - Ono, Chikako

AU - Nakamura, Shota

AU - Motooka, Daisuke

AU - Mori, Hiroyuki

AU - Kurihara, Takeshi

AU - Sato, Asuka

AU - Tamura, Tomokazu

AU - Motomura, Takashi

AU - Okamoto, Toru

AU - Imamura, Michio

AU - Ikegami, Toru

AU - Yoshizumi, Tomoharu

AU - Soejima, Yuji

AU - Maehara, Yoshihiko

AU - Chayama, Kazuaki

AU - Matsuura, Yoshiharu

PY - 2017/3/22

Y1 - 2017/3/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85016080611&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016080611&partnerID=8YFLogxK

U2 - 10.1038/srep45228

DO - 10.1038/srep45228

M3 - Article

C2 - 28327559

AN - SCOPUS:85016080611

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 45228

ER -