Activation of the interferon-inducible 2'-5'-oligoadenylate synthetase gene by hepatitis C virus core protein

A. Naganuma, A. Nozaki, T. Tanaka, K. Sugiyama, H. Takagi, M. Mori, K. Shimotohno, Nobuyuki Kato

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The effects of hepatitis C virus (HCV) proteins on several signal transduction pathways in human nonneoplastic hepatocyte PH5CH8 cells were investigated using expression vectors encoding HCV proteins derived from HCV-infected human nonneoplastic cultured T-lymphocyte and hepatocyte cells (MT-2C and PH5CH7), which could support HCV replication. The amino acid sequences of HCV proteins obtained from HCV-infected human cells were identical or very close to the consensus sequences of the proteins derived from the original inoculum used for HCV infection. During the course of the study, we found that HCV core protein specifically activated the 40/46-kDa 2'-5'-oligoadenylate synthetase (2'-5'-OAS) gene promoter in a dose-dependent manner in different human hepatocyte cell lines (PH5CH8, HepG2, and PLC/PRF/5). We also found that the activation by core protein was further enhanced in the cells treated with alpha interferon. The expression of E1 or E2 envelope protein or nonstructural NS5A protein did not activate the 2'-5'-OAS gene promoter. We demonstrated that the activation by core protein in the hepatocyte cells was suppressed by antisense RNA complementary to core-encoding RNA. Deletion mutant analysis of core protein and deletion analysis of the 2'-5'-OAS gene promoter have been performed. Finally, we demonstrated that the activation of the 2'-5'-OAS gene occurred at the transcriptional level and furthermore demonstrated that the endogenous 2'-5'-OAS gene was also activated by core protein. This is the first report to show that a viral protein activated the 2'-5'-OAS gene.

Original languageEnglish
Pages (from-to)8744-8750
Number of pages7
JournalJournal of Virology
Volume74
Issue number18
DOIs
Publication statusPublished - 2000

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Hepatitis C virus
interferons
Ligases
ligases
Interferons
Hepacivirus
Genes
Proteins
genes
proteins
Hepatocytes
hepatocytes
promoter regions
cells
2',5'-oligoadenylate
Hepatitis C virus nucleocapsid protein
Antisense RNA
antisense RNA
interferon-alpha
Consensus Sequence

ASJC Scopus subject areas

  • Immunology

Cite this

Activation of the interferon-inducible 2'-5'-oligoadenylate synthetase gene by hepatitis C virus core protein. / Naganuma, A.; Nozaki, A.; Tanaka, T.; Sugiyama, K.; Takagi, H.; Mori, M.; Shimotohno, K.; Kato, Nobuyuki.

In: Journal of Virology, Vol. 74, No. 18, 2000, p. 8744-8750.

Research output: Contribution to journalArticle

Naganuma, A, Nozaki, A, Tanaka, T, Sugiyama, K, Takagi, H, Mori, M, Shimotohno, K & Kato, N 2000, 'Activation of the interferon-inducible 2'-5'-oligoadenylate synthetase gene by hepatitis C virus core protein', Journal of Virology, vol. 74, no. 18, pp. 8744-8750. https://doi.org/10.1128/JVI.74.18.8744-8750.2000
Naganuma, A. ; Nozaki, A. ; Tanaka, T. ; Sugiyama, K. ; Takagi, H. ; Mori, M. ; Shimotohno, K. ; Kato, Nobuyuki. / Activation of the interferon-inducible 2'-5'-oligoadenylate synthetase gene by hepatitis C virus core protein. In: Journal of Virology. 2000 ; Vol. 74, No. 18. pp. 8744-8750.
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