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The N- and C-terminal domains of the NS1 protein of influenza B virus can independently inhibit IRF-3 and beta interferon promoter activation
被引:65
作者:
Donelan, NR
Dauber, B
Wang, XY
Basler, CF
Wolff, T
García-Sastre, A
机构:
[1] CUNY Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA
[2] CUNY Mt Sinai Sch Med, Microbiol Grad Sch, Training Program, New York, NY 10029 USA
[3] Robert Koch Inst, Berlin, Germany
关键词:
D O I:
10.1128/JVI.78.21.11574-11582.2004
中图分类号:
Q93 [微生物学];
学科分类号:
071005 ;
100705 ;
摘要:
The NS1 proteins of influenza A and B viruses (A/NS1 and B/NS1 proteins) have only similar to20% 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.
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页码:11574 / 11582
页数:9
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