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Strain-to-strain difference of V protein of measles virus affects MDA5-mediated IFN-β-inducing potential

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Title: Strain-to-strain difference of V protein of measles virus affects MDA5-mediated IFN-β-inducing potential
Authors: Takaki, Hiromi Browse this author
Watanabe, Yumi Browse this author
Shingai, Masashi Browse this author
Oshiumi, Hiroyuki Browse this author
Matsumoto, Misako Browse this author
Seya, Tsukasa Browse this author
Keywords: Measles virus
V protein
MDA5
IRF-3
Interferon-beta
Issue Date: Jan-2011
Publisher: Elsevier
Journal Title: Molecular Immunology
Volume: 48
Issue: 4
Start Page: 497
End Page: 504
Publisher DOI: 10.1016/j.molimm.2010.10.006
PMID: 21071089
Abstract: Laboratory-adapted and vaccine strains of measles virus (MV) induce type I interferon (IFN) in infected cells to a far greater extent than wild-type strains. We investigated the mechanisms for this differential type I IFN production in cells infected with representative MV strains. The overexpression of the wild-type V protein suppressed melanoma differentiation-associated gene 5 (MDA5)-induced IFN-β promoter activity, while this was not seen in A549 cells expressing CD150 transfected with the V protein of the vaccine strain. The V proteins of the wild-type also suppressed poly I:C-induced IFN regulatory factor 3 (IRF-3) dimerization. The V proteins of the wild-type and vaccine strain did not affect retinoic acid-inducible gene 1 (RIG-I)- or toll-IL-1R homology domain-containing adaptor molecule 1 (TICAM-1)-induced IFN-β promoter activation. We identified an amino acid substitution of the cysteine residue at position 272 (which is conserved among paramyxoviruses) to an arginine residue in the V protein of the vaccine strain. Only the V protein possessing the 272C residue binds to MDA5. The mutation introduced into the wild-type V protein (C272R) was unable to suppress MDA5-induced IRF-3 nuclear translocation and IFN-β promoter activation as seen in the V proteins of the vaccine strain, whereas the mutation introduced in the vaccine strain V protein (R272C) was able to inhibit MDA5-induced IRF-3 and IFN-β promoter activation. The other 6 residues of the vaccine strain V sequence inconsistent with the authentic sequence of the wild-type V protein barely affected the IRF-3 nuclear translocation. These data suggested that the structural difference of vaccine MV V protein hampers MDA5 blockade and acts as a nidus for the spread/amplification of type I IFN induction. Ultimately, measles vaccine strains have two modes of IFN-β-induction for their attenuation: V protein mutation and production of defective interference (DI) RNA.
Type: article (author version)
URI: http://hdl.handle.net/2115/45010
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 瀬谷 司

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