The N- and C-terminal domains of the NS1 protein of influenza B virus can independently inhibit IRF-3 and beta interferon promoter activation.
The NS1 proteins of influenza A and B viruses (A/NS1 and B/NS1 proteins) have only approximately 20% amino acid sequence identity. Nevertheless, these proteins show several functional similarities, such as their ability to bind to the same RNA targets and to inhibit the activation of protein kinase R in vitro. A critical function of the A/NS1 protein is the inhibition of synthesis of alpha/beta interferon (IFN-alpha/beta) during viral infection. Recently, it was also found that the B/NS1 protein inhibits IFN-alpha/beta synthesis in virus-infected cells. We have now found that the expression of the B/NS1 protein complements the growth of an influenza A virus with A/NS1 deleted. Expression of the full-length B/NS1 protein (281 amino acids), as well as either its N-terminal RNA-binding domain (amino acids 1 to 93) or C-terminal domain (amino acids 94 to 281), in the absence of any other influenza B virus proteins resulted in the inhibition of IRF-3 nuclear translocation and IFN-beta promoter activation. A mutational analysis of the truncated B/NS1(1-93) protein showed that RNA-binding activity correlated with IFN-beta promoter inhibition. In addition, a recombinant influenza B virus with NS1 deleted induces higher levels of IRF-3 activation, as determined by its nuclear translocation, and of IFN-alpha/beta synthesis than wild-type influenza B virus. Our results support the hypothesis that the NS1 protein of influenza B virus plays an important role in antagonizing the IRF-3- and IFN-induced antiviral host responses to virus infection.
Donelan
Nicola R
NR
Department of Microbiology, Box 1124, Mount Sinai School of Medicine, 1 Gustave L. Levy Pl., New York, NY 10029, USA.
Dauber
Bianca
B
Wang
Xiuyan
X
Basler
Christopher F
CF
Wolff
Thorsten
T
García-Sastre
Adolfo
A
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D009981:Influenza B virus / Q000737:chemistry / Q000502:physiology*; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000235:genetics; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D012313:RNA / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000502:physiology*
D004268:DNA-Binding Proteins; C085820:INS1 protein, influenza virus; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D014157:Transcription Factors; D017361:Viral Nonstructural Proteins; D012313:RNA; D016899:Interferon-beta