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

Interestingly, strain-specific targeting of TRAF3 was demonstrated by specific interaction of NS1 proteins encoded by PR8 or avian H5N1 but not novel H7N9 or avian H9N2 viruses. This difference may be associated with strain-specific sequence variations. The NS1 protein most often occurs as a 230 residue peptide, including NS1 of seasonal H1N1 virus and avian H5N1 virus (80-84 residues have been deleted since 2000), which were used in this study. However, premature stop codons or, alternatively, suppression of the genuine stop codon (codon 231) resulted in length variations at NS1's C-terminus. Abdelwhab et al. analyzed NS1 protein sequences of all AIV subtypes in birds from 1902 to 2015 to study the prevalence and distribution of carboxyl terminal end truncation (ΔCTE). They found that NS217 proteins lacking amino acids 218-230 were the most prevalent form (88%). This truncation is prevalent in LPAIV of non-H5/H7 subtypes; particularly H9N2, H10, and H6 viruses that are known to be widespread and mostly (semi)endemic in land-based poultry (54) . Similar truncations have also been observed in swine influenza viruses, which harbor a C-terminally truncated NS1 and have also been found in human H1N1 viruses that have been in public circulation since the 2009 pandemic (55) . Hence, whether the interaction of NS1 and TRAF3 are associated with the ΔCTE requires further investigation.