A C-terminal basic amino acid motif of Zaire ebolavirus VP35 is essential for type I interferon antagonism and displays high identity with the RNA-binding domain of another interferon antagonist, the NS1 protein of influenza A virus.
The ebolavirus VP35 protein antagonizes the cellular type I interferon response by blocking phosphorylation of IRF-3, a transcription factor that turns on the expression of a large number of antiviral genes. To identify the domain of VP35 responsible for interferon antagonism, we generated mutations within the VP35 gene and found that a C-terminal basic amino acid motif is required for inhibition of ISG56 reporter gene expression as well as IFN-beta production. Remarkably, this basic amino acid motif displayed high sequence identity with part of the N-terminal RNA-binding domain of another interferon-antagonist, the NS1 protein of influenza A virus.
Special Pathogens Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road MS G-14 Atlanta, GA 30329, USA. biq7@cdc.gov
Amy L
AL
Hartman
Jonathan S
JS
Towner
Stuart T
ST
Nichol
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029043:Ebolavirus / Q000737:chemistry / Q000276:immunology*; D017930:Genes, Reporter; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000235:genetics; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
D004268:DNA-Binding Proteins; C085820:INS1 protein, influenza virus; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C080980:VP35 protein, filovirus; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins