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MDA5 detects the double-stranded RNA replicative form in picornavirus-infected cells.

Authors
  • Feng, Qian1
  • Hato, Stanleyson V
  • Langereis, Martijn A
  • Zoll, Jan
  • Virgen-Slane, Richard
  • Peisley, Alys
  • Hur, Sun
  • Semler, Bert L
  • van Rij, Ronald P
  • van Kuppeveld, Frank J M
  • 1 Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, PO Box 9101, 6500 HB, The Netherlands. , (Netherlands)
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
Nov 29, 2012
Volume
2
Issue
5
Pages
1187–1196
Identifiers
DOI: 10.1016/j.celrep.2012.10.005
PMID: 23142662
Source
Medline
Language
English
License
Unknown

Abstract

RIG-I and MDA5 are cytosolic RNA sensors that play a critical role in innate antiviral responses. Major advances have been made in identifying RIG-I ligands, but our knowledge of the ligands for MDA5 remains restricted to data from transfection experiments mostly using poly(I:C), a synthetic dsRNA mimic. Here, we dissected the IFN-α/β-stimulatory activity of different viral RNA species produced during picornavirus infection, both by RNA transfection and in infected cells in which specific steps of viral RNA replication were inhibited. Our results show that the incoming genomic plus-strand RNA does not activate MDA5, but minus-strand RNA synthesis and production of the 7.5 kbp replicative form trigger a strong IFN-α/β response. IFN-α/β production does not rely on plus-strand RNA synthesis and thus generation of the partially double-stranded replicative intermediate. This study reports MDA5 activation by a natural RNA ligand under physiological conditions. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

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