PA-X is a fusion protein encoded by a +1 frameshifted open reading frame (X-ORF) in PA gene. The X-ORF can be translated in full-length (61 amino acids, aa) or truncated (41 aa) form. However, the role of C-Terminal 20 aa of PA-X in virus function has not yet been fully elucidated. To this end, we constructed the contemporary influenza viruses with full and truncated PA-X by reverse genetics to compare their replication and pathogenicity. The full-length PA-X virus in MDCK and human A549 cells conferred 10- to 100-fold increase in viral replication, and more virulent and caused more severe inflammatory responses in mice relative to corresponding truncated PA-X virus, suggesting that the terminal 20 aa could play a role in enhancing viral replication and contribute to virulence.

PA-X是一种融合蛋白，由PA基因中的+1移码开放阅读框（X-ORF）编码。X-ORF可以全长（61个氨基酸，aa）或截短（41aa）的形式翻译。但是，PA-X的C末端20aa在病毒功能中的作用尚未完全阐明。为此，我们通过反向遗传学构建了具有完整和截短的PA-X的当代流感病毒，以比较它们的复制和致病性。与相应的截短的PA-X病毒相比，MDCK和人A549细胞中的全长PA-X病毒使病毒复制增加10至100倍，并且更具毒性，并引起更严重的炎症反应，提示小鼠20氨基酸可能在增强病毒复制和促进毒力中发挥作用。