Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity Gao, Huijie and Sun, Honglei and Hu, Jiao and Qi, Lu and Wang, Jinliang and Xiong, Xin and Wang, Yu and He, Qiming and Lin, Yang and Kong, Weili and Seng, Lai-Giea and Pu, Juan and Chang, Kin-Chow and Liu, Xiufan and Liu, Jinhua and Sun, Yipeng,, 96, 2036-2049 (2015), doi = https://doi.org/10.1099/vir.0.000143, publicationName = Microbiology Society, issn = 0022-1317, abstract= 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., language=, type=