Replication of subgenomic hepatitis C virus replicons in mouse fibroblasts is facilitated by deletion of interferon regulatory factor 3 and expression of liver-specific microRNA 122

Liang Tzung Lin, Ryan S. Noyce, Tram N Q Pham, Joyce A. Wilson, Gary R. Sisson, Thomas I. Michalak, Karen L. Mossman, Christopher D. Richardson

Research output: Contribution to journalArticle

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Abstract

Hepatitis C virus (HCV) infection causes significant morbidity, and efficient mouse models would greatly facilitate virus studies and the development of effective vaccines and new therapeutic agents. Entry factors, innate immunity, and host factors needed for viral replication represent the initial barriers that restrict HCV infection of mouse cells. Experiments in this paper consider early postentry steps of viral infection and investigate the roles of interferon regulatory factors (IRF-3 and IRF-9) and microRNA (miR-122) in promoting HCV replication in mouse embryo fibroblasts (MEFs) that contain viral subgenomic replicons. While wild-type murine fibroblasts are restricted for HCV RNA replication, deletion of IRF-3 alone can facilitate replicon activity in these cells. This effect is thought to be related to the inactivation of the type I interferon synthesis mediated by IRF-3. Additional deletion of IRF-9 to yield IRF-3-/- IRF-9-/- MEFs, which have blocked type I interferon signaling, did not increase HCV replication. Expression of liver-specific miR-122 in MEFs further stimulated the synthesis of HCV replicons in the rodent fibroblasts. The combined effects of miR-122 expression and deletion of IRF-3 produced a cooperative stimulation of HCV subgenome replication. miR-122 and IRF-3 are independent host factors that are capable of influencing HCV replication, and our findings could help to establish mouse models and other cell systems that support HCV growth and particle formation.

Original languageEnglish
Pages (from-to)9170-9180
Number of pages11
JournalJournal of Virology
Volume84
Issue number18
DOIs
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

Interferon Regulatory Factor-3
replicon
Replicon
Hepatitis C virus
MicroRNAs
microRNA
Hepacivirus
fibroblasts
Fibroblasts
liver
Virus Replication
virus replication
Liver
mice
Virus Diseases
Interferon Type I
embryo (animal)
Embryonic Structures
interferons
animal models

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Medicine(all)

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Replication of subgenomic hepatitis C virus replicons in mouse fibroblasts is facilitated by deletion of interferon regulatory factor 3 and expression of liver-specific microRNA 122. / Lin, Liang Tzung; Noyce, Ryan S.; Pham, Tram N Q; Wilson, Joyce A.; Sisson, Gary R.; Michalak, Thomas I.; Mossman, Karen L.; Richardson, Christopher D.

In: Journal of Virology, Vol. 84, No. 18, 2010, p. 9170-9180.

Research output: Contribution to journalArticle

Lin, Liang Tzung ; Noyce, Ryan S. ; Pham, Tram N Q ; Wilson, Joyce A. ; Sisson, Gary R. ; Michalak, Thomas I. ; Mossman, Karen L. ; Richardson, Christopher D. / Replication of subgenomic hepatitis C virus replicons in mouse fibroblasts is facilitated by deletion of interferon regulatory factor 3 and expression of liver-specific microRNA 122. In: Journal of Virology. 2010 ; Vol. 84, No. 18. pp. 9170-9180.
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