Novel type I interferon IL-28A suppresses hepatitis C viral RNA replication

Haizhen Zhu, Mike Butera, David R. Nelson, Chen Liu

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Interferon alpha (IFN-α)-based therapy is the currently approved treatment for chronic hepatitis C viral infection. The sustained antiviral response rate is approximately 50% for genotype-1 infection. The major challenge to the HCV community is to improve antiviral efficacy and to reduce the side effects typically seen in IFNα-based therapy. One of the strategies is to identify new interferons, which may have better efficacy and less undesirable side effects. In this report, we examined the role of IL-28A (IFN λ2), a novel type I IFN, in suppression of human hepatitis C viral RNA replication. We have cloned both the human genomic DNA and cDNA of IL-28A, and evaluated their biological activity using HCV RNA replicon cell culture system. The results show that IL-28A effectively inhibits HCV subgenomic RNA replication in a dose-dependent manner. Treatment of human hepatoma cells with IL-28A activates the JAK-STAT signaling pathway and induces the expression of some interferon-stimulated genes (ISGs), such as 6-16 and 1-8U. We also demonstrate that IL-28A induces expression of HLA class I antigens in human hepatoma cells. Moreover, IL-28A appears to specifically suppress HCV IRES-mediated translation. Although IL-28A receptor shares one subunit with the IL-10 receptor, IL-10 treatment has no detectable effect on IL-28A-induced antiviral activity. Interestingly, IL-28A can synergistically enhance IFNα antiviral efficacy. Our results suggest that IL-28A antiviral activity is associated with the activation of the JAK-STAT signaling pathway and expression of ISGs. The effectiveness of IL-28A antiviral activity and its synergistic effect on IFN-α indicate that IL-28A may be potentially used to treat HCV chronic infection.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalVirology Journal
Volume2
DOIs
StatePublished - Sep 7 2005

Fingerprint

Interferon Type I
Viral RNA
Hepatitis C
Antiviral Agents
Interferon-alpha
Interferons
Hepatocellular Carcinoma
Interleukin-10 Receptors
RNA
Histocompatibility Antigens Class I
Replicon
Chronic Hepatitis C
Virus Diseases
HLA Antigens
Infection
Interleukin-10
Genes
Complementary DNA
Cell Culture Techniques
Genotype

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

Cite this

Zhu, Haizhen ; Butera, Mike ; Nelson, David R. ; Liu, Chen. / Novel type I interferon IL-28A suppresses hepatitis C viral RNA replication. In: Virology Journal. 2005 ; Vol. 2. pp. 1-12.
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Novel type I interferon IL-28A suppresses hepatitis C viral RNA replication. / Zhu, Haizhen; Butera, Mike; Nelson, David R.; Liu, Chen.

In: Virology Journal, Vol. 2, 07.09.2005, p. 1-12.

Research output: Contribution to journalArticle

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