The role of PA-X C-terminal 20 residues of classical swine influenza virus in its replication and pathogenicity.

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.