Interferon resistance of hepatitis C virus replicon-harbouring cells is caused by functional disruption of type I interferon receptors

Kazuhito Naka, Kazunori Takemoto, Ken Ichi Abe, Hiromichi Dansako, Masanori Ikeda, Kunitada Shimotohno, Nobuyuki Kato

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) replicon-harbouring cell lines possessing interferon (IFN)-resistant phenotypes have recently been established. These were divided into two classes: partially IFN resistant and highly IFN resistant. Here, the viral and cellular factors contributing to the IFN resistance of HCV replicon-harbouring cells were evaluated. The results revealed that cellular factors rather than viral factors contributed to a highly IFN-resistant phenotype. The possibility of genetic abnormality of the factors involved in IFN signalling was investigated. As a result, nonsense mutations and deletions in type I IFN receptor genes (IFNAR1 and IFNAR2c) were found in replicon-harbouring cells showing a highly IFN-resistant phenotype, but rarely appeared in cells showing a partially IFN-resistant phenotype. Furthermore, similar genetic alterations were also found in IFN-resistant phenotype, replicon-harbouring cell lines obtained additionally by IFN-β treatment. Moreover, it was shown that ectopic expression of wild-type IFNAR1 in IFN-resistant phenotype, replicon-harbouring cells possessing the IFNAR1 mutant restored type I IFN signalling.

Original languageEnglish
Pages (from-to)2787-2792
Number of pages6
JournalJournal of General Virology
Volume86
Issue number10
DOIs
Publication statusPublished - Oct 2005

ASJC Scopus subject areas

  • Virology

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