The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-ß Production by Targeting TNF Receptor-Associated Factor 3

Qian, Wei; Wei, Xiaoqin; Guo, Kelei; Li, Yongtao; Lin, Xian; Zou, Zhong; Zhou, Hongbo; Jin, Meilin

In another similar pathway, NS1 has been shown to inhibit host mRNA synthesis by binding a cellular 3′ end-processing factor, the 30 kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), thus attenuating type I interferon (IFN-α/β) and other interferon stimulated gene (ISG) mRNAs that are involved in the antiviral response (21) . The NS1 proteins encoded by the seasonal H1N1, H2N2, H3N2, and avian H5N1 viral subtypes strongly bind to CPSF30 (22) , whereas PR8, 2009 pandemic H1N1, and novel H7N9 virus do not efficiently bind CPSF30 (23) . It is noteworthy that cells infected with viruses expressing NS1 proteins in seasonal H3N2 and H2N2 viruses do not inhibit IRF3 activation. However, activation is blocked in cells infected with viruses expressing NS1 proteins in some, but not all, seasonal H1N1 viruses, 2009 pandemic H1N1, and avian H5N1 viruses. TRIM25 was previously reported to interact with each of these NS1 proteins, whether or not they block IRF3 activation, indicating that binding of TRIM25 by the NS1 protein does not necessarily lead to blocking of IRF3 activation (22) . Hence, binding of the NS1 protein to dsRNA, RIG-I, and TRIM25 has not established that these NS1 interactions are responsible for inhibiting the activation of IRF3 and IFN transcription. In this case, one or more host factors may participate in the NS1 blocking of IRF3 activation.