Paramyxovirus V Proteins Interact with the RNA Helicase LGP2 To Inhibit RIG-I-Dependent Interferon Induction

Journal of Virology - Tập 86 Số 7 - Trang 3411-3421 - 2012
Kay Childs1, Richard E. Randall2, Stephen Goodbourn1
1Division of Basic Medical Sciences, St. George's, University of London, London, United Kingdom.
2Biomolecular Sciences Building, School of Biology, University of St. Andrews, North Haugh, St. Andrews, United Kingdom

Tóm tắt

ABSTRACT RIG-I and mda-5 are activated by viral RNA and stimulate type I interferon production. Laboratory of genetics and physiology 2 (LGP2) shares homology with RIG-I and mda-5 but lacks the CARD domains required for signaling. The V proteins of paramyxoviruses limit interferon induction by binding mda-5 and preventing its activation; however, they do not bind RIG-I and have not been considered inhibitors of RIG-I signaling. Here we uncover a novel mechanism of RIG-I inhibition in which the V protein of parainfluenzavirus type 5 (PIV5; formerly known as simian virus type 5 [SV5]) interacts with LGP2 and cooperatively inhibits induction by RIG-I ligands. A complex between RIG-I and LGP2 is observed in the presence of PIV5-V, and we propose that this complex is refractory to activation by RIG-I ligands. The V proteins from other paramyxoviruses also bind LGP2 and demonstrate LGP2-dependent inhibition of RIG-I signaling. This is significant, because it demonstrates a general mechanism for the targeting of the RIG-I pathway by paramyxoviruses.

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