Analysis of interaction of Sendai virus V protein and melanoma differentiation-associated gene 5.

Abstract

Sendai virus (SeV), a pneumotropic virus of rodents, has an accessory protein, V, and the V protein has been shown to interact with MDA5, inhibiting IRF3 activation and interferon-β production. In the present study, interaction of the V protein with various IRF3-activating proteins including MDA5 was investigated in a co-immunoprecipitation assay. We also investigated interaction of mutant V proteins from SeVs of low pathogenicity with MDA5. The V protein interacted with at least retinoic acid inducible gene I, inhibitor of κB kinase epsilon and IRF3 other than MDA5. However, only MDA5 interacted with the V protein dependently on the C-terminal V unique (Vu) region, inhibiting IRF3 reporter activation. The Vu region has been shown to be important for viral pathogenicity. We thus focused on interaction of the V protein with MDA5. Point mutations in the Vu region destabilized the V protein or abolished the interaction with MDA5 when the V protein was stable. The V-R₃₂₀G protein was highly stable and interacted with MDA5, but did not inhibit activation of IRF3 induced by MDA5. Viral pathogenicity of SeV is related to the inhibitory effect of the V protein on MDA5, but is not always related to the binding of V protein with MDA5.

• Authors: Takemasa Sakaguchi, Takashi Irie, Masaru Kuwayama, Tatsuya Ueno, Asuka Yoshida, Ryoko Kawabata
• Journal: Microbiology and immunology (Microbiol Immunol) Vol. 55 Issue 11 Pg. 760-7 (Nov 2011) ISSN: 1348-0421 [Electronic] Australia
• PMID: 21851384 (Publication Type: Journal Article)
• Copyright: © 2011 The Societies and Blackwell Publishing Asia Pty Ltd.

Chemical References

• Interferon Regulatory Factor-3
• Irf3 protein, mouse
• Mutant Proteins
• Rai1 protein, mouse
• Trans-Activators
• V protein, Sendai virus
• Viral Proteins
• Ifih1 protein, mouse
• DEAD-box RNA Helicases
• Interferon-Induced Helicase, IFIH1

Topics

• Animals
• Cell Line
• DEAD-box RNA Helicases (metabolism)
• Humans
• Immunoprecipitation
• Interferon Regulatory Factor-3 (metabolism)
• Interferon-Induced Helicase, IFIH1
• Mice
• Mutant Proteins (genetics, metabolism)
• Protein Binding
• Protein Interaction Mapping
• Trans-Activators (metabolism)
• Viral Proteins (genetics, metabolism)