PMID:22532687

Citation	Irie, T, Kiyotani, K, Igarashi, T, Yoshida, A and Sakaguchi, T (2012) Inhibition of interferon regulatory factor 3 activation by paramyxovirus V protein. J. Virol. 86:7136-45
Abstract	The V protein of Sendai virus (SeV) suppresses innate immunity, resulting in enhancement of viral growth in mouse lungs and viral pathogenicity. The innate immunity restricted by the V protein is induced through activation of interferon regulatory factor 3 (IRF3). The V protein has been shown to interact with melanoma differentiation-associated gene 5 (MDA5) and to inhibit beta interferon production. In the present study, we infected MDA5-knockout mice with V-deficient SeV and found that MDA5 was largely unrelated to the innate immunity that the V protein suppresses in vivo. We therefore investigated the target of the SeV V protein. We previously reported interaction of the V protein with IRF3. Here we extended the observation and showed that the V protein appeared to inhibit translocation of IRF3 into the nucleus. We also found that the V protein inhibited IRF3 activation when induced by a constitutive active form of IRF3. The V proteins of measles virus and Newcastle disease virus inhibited IRF3 transcriptional activation, as did the V protein of SeV, while the V proteins of mumps virus and Nipah virus did not, and inhibition by these proteins correlated with interaction of each V protein with IRF3. These results indicate that IRF3 is important as an alternative target of paramyxovirus V proteins.
Links	PubMed PMC3416347 Online version:10.1128/JVI.06705-11
Keywords	Animals; DEAD-box RNA Helicases/deficiency; DEAD-box RNA Helicases/immunology; Immune Evasion; Interferon Regulatory Factor-3/antagonists & inhibitors; Interferon Regulatory Factor-3/immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Phosphoproteins/immunology; Phosphoproteins/metabolism; Sendai virus/immunology; Sendai virus/pathogenicity; Viral Proteins/genetics; Viral Proteins/immunology; Viral Proteins/metabolism; Viral Structural Proteins/immunology; Viral Structural Proteins/metabolism; Virulence Factors/deficiency; Virulence Factors/immunology; Virulence Factors/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
SENDZ:V		GO:0039503: suppression by virus of host innate immune response	ECO:0000315:		P		Table 1 reveals the decreased prevelance of virus in mice infected with virus lacking the V protein gene. Background information supports the connection of V protein to suppression of immune response.	complete CACAO 6740
SENDZ:V		GO:0044164: host cell cytosol	ECO:0000314:		C		Fig.4	complete CACAO 7186
SENDZ:V		GO:0039548: suppression by virus of host IRF3 activity	ECO:0000314:		P		Fig 6, 7 & 9.	complete CACAO 7295
SENDZ:V	involved_in	GO:0039503: suppression by virus of host innate immune response	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
SENDZ:V	involved_in	GO:0039548: suppression by virus of host IRF3 activity	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
SENDZ:V	part_of	GO:0044164: host cell cytosol	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete

References

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