RT Journal Article SR Electronic(1) A1 Gao, Huijie A1 Sun, Honglei A1 Hu, Jiao A1 Qi, Lu A1 Wang, Jinliang A1 Xiong, Xin A1 Wang, Yu A1 He, Qiming A1 Lin, Yang A1 Kong, Weili A1 Seng, Lai-Giea A1 Pu, Juan A1 Chang, Kin-Chow A1 Liu, Xiufan A1 Liu, Jinhua A1 Sun, YipengYR 2015 T1 Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity JF Journal of General Virology, VO 96 IS 8 SP 2036 OP 2049 DO https://doi.org/10.1099/vir.0.000143 PB Microbiology Society, SN 1465-2099, AB The PA-X protein, arising from ribosomal frameshift during PA translation, was recently discovered in influenza A virus (IAV). The C-terminal domain ‘X’ of PA-X proteins in IAVs can be classified as full-length (61 aa) or truncated (41 aa). In the main, avian influenza viruses express full-length PA-X proteins, whilst 2009 pandemic H1N1 (pH1N1) influenza viruses harbour truncated PA proteins. The truncated form lacks aa 232–252 of the full-length PA-X protein. The significance of PA-X length in virus function remains unclear. To address this issue, we constructed a set of contemporary influenza viruses (pH1N1, avian H5N1 and H9N2) with full and truncated PA-X by reverse genetics to compare their replication and host pathogenicity. All full-length PA-X viruses in human A549 cells conferred 10- to 100-fold increase in viral replication and 5–8 % increase in apoptosis relative to corresponding truncated PA-X viruses. Full-length PA-X viruses were more virulent and caused more severe inflammatory responses in mice. Furthermore, aa 233–252 at the C terminus of PA-X strongly suppressed co-transfected gene expression by ∼50 %, suggesting that these terminal 20 aa could play a role in enhancing viral replication and contribute to virulence., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.000143