Paramyxovirus V proteins interact with the RNA Helicase LGP2 to inhibit RIG-I-dependent interferon induction.
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.
Division of Basic Medical Sciences, St. George’s, University of London, London, United Kingdom. s.goodbourn@sgul.ac.uk
Kay
K
Childs
Richard
R
Randall
Stephen
S
Goodbourn
D000595:Amino Acid Sequence; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D007372:Interferons / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D020365:RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic; D019213:Rubulavirus / Q000235:genetics / Q000378:metabolism*; D019351:Rubulavirus Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D016415:Sequence Alignment; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D011971:Receptors, Immunologic; C502891:V protein, Paramyxovirus; D014764:Viral Proteins; D016899:Interferon-beta; D007372:Interferons; C520569:DHX58 protein, human; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases