Expression of microRNA miR-122 facilitates an efficient replication in nonhepatic cells upon infection with hepatitis C virus

Takasuke Fukuhara, Hiroto Kambara, Mai Shiokawa, Chikako Ono, Hiroshi Katoh, Eiji Morita, Daisuke Okuzaki, Yoshihiko Maehara, Kazuhiko Koike, Yoshiharu Matsuura

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Abstract

Hepatitis C virus (HCV) is one of the most common etiologic agents of chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma. In addition, HCV infection is often associated with extrahepatic manifestations (EHM), including mixed cryoglobulinemia and non-Hodgkin's lymphoma. However, the mechanisms of cell tropism of HCV and HCV-induced EHM remain elusive, because in vitro propagation of HCV has been limited in the combination of cell culture-adapted HCV (HCVcc) and several hepatic cell lines. Recently, a liver-specific microRNA called miR-122 was shown to facilitate the efficient propagation of HCVcc in several hepatic cell lines. In this study, we evaluated the importance of miR-122 on the replication of HCV in nonhepatic cells. Among the nonhepatic cell lines expressing functional HCV entry receptors, Hec1B cells derived from human uterus exhibited a low level of replication of the HCV genome upon infection with HCVcc. Exogenous expression of miR-122 in several cells facilitates efficient viral replication but not production of infectious particles, probably due to the lack of hepatocytic lipid metabolism. Furthermore, expression of mutant miR-122 carrying a substitution in a seed domain was required for efficient replication of mutant HCVcc carrying complementary substitutions in miR-122-binding sites, suggesting that specific interaction between miR-122 and HCV RNA is essential for the enhancement of viral replication. In conclusion, although miR-122 facilitates efficient viral replication in nonhepatic cells, factors other than miR-122, which are most likely specific to hepatocytes, are required for HCV assembly.

Original languageEnglish
Pages (from-to)7918-7933
Number of pages16
JournalJournal of virology
Volume86
Issue number15
DOIs
Publication statusPublished - Aug 2 2012

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Hepatitis C virus
MicroRNAs
microRNA
Hepacivirus
Infection
infection
cells
virus replication
hepatocytes
Hepatocytes
cell lines
Cell Line
Non-Hodgkin's Lymphoma
non-Hodgkin lymphoma
Virus Receptors
Virus Assembly
Cryoglobulinemia
Virus Internalization
mutants
tropisms

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Fukuhara, T., Kambara, H., Shiokawa, M., Ono, C., Katoh, H., Morita, E., ... Matsuura, Y. (2012). Expression of microRNA miR-122 facilitates an efficient replication in nonhepatic cells upon infection with hepatitis C virus. Journal of virology, 86(15), 7918-7933. https://doi.org/10.1128/JVI.00567-12

Expression of microRNA miR-122 facilitates an efficient replication in nonhepatic cells upon infection with hepatitis C virus. / Fukuhara, Takasuke; Kambara, Hiroto; Shiokawa, Mai; Ono, Chikako; Katoh, Hiroshi; Morita, Eiji; Okuzaki, Daisuke; Maehara, Yoshihiko; Koike, Kazuhiko; Matsuura, Yoshiharu.

In: Journal of virology, Vol. 86, No. 15, 02.08.2012, p. 7918-7933.

Research output: Contribution to journalArticle

Fukuhara, T, Kambara, H, Shiokawa, M, Ono, C, Katoh, H, Morita, E, Okuzaki, D, Maehara, Y, Koike, K & Matsuura, Y 2012, 'Expression of microRNA miR-122 facilitates an efficient replication in nonhepatic cells upon infection with hepatitis C virus', Journal of virology, vol. 86, no. 15, pp. 7918-7933. https://doi.org/10.1128/JVI.00567-12
Fukuhara, Takasuke ; Kambara, Hiroto ; Shiokawa, Mai ; Ono, Chikako ; Katoh, Hiroshi ; Morita, Eiji ; Okuzaki, Daisuke ; Maehara, Yoshihiko ; Koike, Kazuhiko ; Matsuura, Yoshiharu. / Expression of microRNA miR-122 facilitates an efficient replication in nonhepatic cells upon infection with hepatitis C virus. In: Journal of virology. 2012 ; Vol. 86, No. 15. pp. 7918-7933.
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