Dissecting the IFN-induced inhibition of hepatitis C virus replication by using a novel host cell line

Marc P. Windisch, Michael Frese, Artur Kaul, Trippler, Volker Lohmann, Ralf Bartenschlager

Research output: Contribution to journalArticle

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Abstract

The Hepatitis C virus (HCV), a member of the family Flaviviridae, is a major cause of chronic liver disease. Patients are currently treated with alpha interferon (IFN-alpha) that is given alone or in combination with ribavirin. Unfortunately, this treatment is ineffective in eliminating the virus in a large proportion of individuals. IFN-induced antiviral activities have been intensively studied in the HCV replicon system. It was found that both IFN-alpha and IFN-gamma inhibit HCV replicons, but the underlying mechanisms have not yet been identified. Of note is that nearly all of these studies were performed with the human hepatoma cell line Huh-7. Here, we report that genotypes 1b and 2a replicons also replicate in the human hepatoblastoma cell line HuH6. Similar to what has been described for Huh-7 cells, we observed that efficient HCV replication in HuH6 cells depends on the presence of cell culture-adaptive mutations and the permissiveness of the host cell. However, three major differences exist: in HuH6 cells, viral replication is (i) independent from ongoing cell proliferation, (ii) less sensitive to certain antiviral compounds, and (iii) highly resistant to IFN-gamma. The latter is not due to a general defect in IFN signaling, as IFN-gamma induces the nuclear translocation of signal transducer and activator of transcription 1 (STAT1), the enhanced transcription of several IFN-regulated genes, and the inhibition of unrelated viruses such as influenza A virus and Semliki Forest virus. Taken together, the results establish HuH6 replicon cells as a valuable tool for IFN studies and for the evaluation of antiviral compounds
Original languageEnglish
Pages (from-to)13778-13793
Number of pages16
JournalJournal of Virology
Volume79
Issue number21
DOIs
Publication statusPublished - 2005
Externally publishedYes

Fingerprint

Hepatitis C virus
Virus Replication
virus replication
replicon
Replicon
Hepacivirus
cell lines
Cell Line
Antiviral Agents
Interferon-alpha
cells
transcription (genetics)
Semliki Forest virus
Flaviviridae
Permissiveness
STAT1 Transcription Factor
Semliki forest virus
Viruses
Hepatoblastoma
viruses

Cite this

Windisch, Marc P. ; Frese, Michael ; Kaul, Artur ; Trippler ; Lohmann, Volker ; Bartenschlager, Ralf. / Dissecting the IFN-induced inhibition of hepatitis C virus replication by using a novel host cell line. In: Journal of Virology. 2005 ; Vol. 79, No. 21. pp. 13778-13793.
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Dissecting the IFN-induced inhibition of hepatitis C virus replication by using a novel host cell line. / Windisch, Marc P.; Frese, Michael; Kaul, Artur; Trippler; Lohmann, Volker; Bartenschlager, Ralf.

In: Journal of Virology, Vol. 79, No. 21, 2005, p. 13778-13793.

Research output: Contribution to journalArticle

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AU - Frese, Michael

AU - Kaul, Artur

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