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J Virol. 2009 Feb;83(3):1465-73. doi: 10.1128/JVI.01768-08. Epub 2008 Nov 19.

Mechanism of mda-5 Inhibition by paramyxovirus V proteins.

Author information

1
Division of Basic Medical Sciences, St. George's, University of London, London SW17 0RE, United Kingdom.

Abstract

The RNA helicases encoded by melanoma differentiation-associated gene 5 (mda-5) and retinoic acid-inducible gene I (RIG-I) detect foreign cytoplasmic RNA molecules generated during the course of a virus infection, and their activation leads to induction of type I interferon synthesis. Paramyxoviruses limit the amount of interferon produced by infected cells through the action of their V protein, which binds to and inhibits mda-5. Here we show that activation of both mda-5 and RIG-I by double-stranded RNA (dsRNA) leads to the formation of homo-oligomers through self-association of the helicase domains. We identify a region within the helicase domain of mda-5 that is targeted by all paramyxovirus V proteins and demonstrate that they inhibit activation of mda-5 by blocking dsRNA binding and consequent self-association. In addition to this commonly targeted domain, some paramyxovirus V proteins target additional regions of mda-5. In contrast, V proteins cannot bind to RIG-I and consequently have no effect on the ability of RIG-I to bind dsRNA or to form oligomers.

PMID:
19019954
PMCID:
PMC2620892
DOI:
10.1128/JVI.01768-08
[Indexed for MEDLINE]
Free PMC Article

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