Type III interferon (IFN-λ) antagonizes the antiviral activity of interferon-α in vitro

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Abstract

Type III interferons (IFN-λ) are the most recently discovered members of IFN family. Synergism between different IFN types is well established, but for type I and type III IFNs no conclusive evidence has been reported so far. Possible synergism/antagonism between IFN-α and IFN-λ in the inhibition of virus replication (EMCV, WNV lineage 1 and 2, CHIKV and HSV-1), and in the activation of intracellular pathways of IFN response (MxA and 2′-5′ OAS) was evaluated in different cell lines (Vero E6, A549 and Wish cells). The antiviral potency of IFN-λ1 and -I2 was lower than that of IFN-α. When IFN-α and -λ were used together, the Combination Index (CI) for virus inhibition was >1 virtually for all virus/host cell systems, indicating antagonistic effect. Antagonism between IFN-α and -I was also observed for the induction of mRNA for both MxA and 2′-5′OAS. Elucidating the interplay between IFN-α and -λ may help to better understand innate defence mechanisms against viral infections, including the molecular mechanisms underlying the influence of IL-28B polymorphisms in the response to HCV and other viral infections.

Original languageEnglish
Pages (from-to)1001-1009
Number of pages9
JournalJournal of Biological Regulators and Homeostatic Agents
Volume27
Issue number4
Publication statusPublished - Oct 2013

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Keywords

  • Antagonism
  • Antiviral activity
  • Combination index
  • IFN-α
  • IFN-λ
  • Interferon-stimulated genes

ASJC Scopus subject areas

  • Oncology
  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Immunology and Allergy
  • Immunology
  • Endocrinology
  • Physiology
  • Cancer Research

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