tetano
Editor, Senior Moderator
Cell Rep
. 2026 Sep 1;45(9):117921.
doi: 10.1016/j.celrep.2026.117921. Online ahead of print.
Kohei Oishi 1 , Kaori Sano 2 , Seiya Yamayoshi 3 , Kei Miyakawa 2 , Hideki Hasegawa 4 , Yoshihiro Kawaoka 5
Affiliations
Influenza A virus protein PA-X mediates host shutoff, yet its molecular mechanism and the role of its C-terminal region remain unclear. When ectopically expressed via plasmids, PA-X cleaves its own mRNAs, leading to remarkably low intracellular expression, which makes its characterization challenging. In this study, we utilize an endonuclease inhibitor to suppress PA-X shutoff activity, enabling its robust expression and purification. Our biochemical analyses reveal that PA-X directly binds RNA via its unique C-terminal basic-rich region and induces mRNA degradation with minimal sequence specificity. Furthermore, we find that while PA-X targets a broad range of RNAs, viral RNAs are protected from its endonuclease activity through their assembly into vRNP complexes. These findings provide critical insights into the PA-X-mediated shutoff strategy, revealing how PA-X modulates the cellular environment while sparing the viral genome to favor viral replication.
Keywords: CP: microbiology; PA-X; endonuclease inhibitor; influenza; shutoff.
. 2026 Sep 1;45(9):117921.
doi: 10.1016/j.celrep.2026.117921. Online ahead of print.
An endonuclease inhibitor unlocks the PA-X shutoff mechanism in influenza A virus
Kohei Oishi 1 , Kaori Sano 2 , Seiya Yamayoshi 3 , Kei Miyakawa 2 , Hideki Hasegawa 4 , Yoshihiro Kawaoka 5
Affiliations
- PMID: 42684885
- DOI: 10.1016/j.celrep.2026.117921
Abstract
Influenza A virus protein PA-X mediates host shutoff, yet its molecular mechanism and the role of its C-terminal region remain unclear. When ectopically expressed via plasmids, PA-X cleaves its own mRNAs, leading to remarkably low intracellular expression, which makes its characterization challenging. In this study, we utilize an endonuclease inhibitor to suppress PA-X shutoff activity, enabling its robust expression and purification. Our biochemical analyses reveal that PA-X directly binds RNA via its unique C-terminal basic-rich region and induces mRNA degradation with minimal sequence specificity. Furthermore, we find that while PA-X targets a broad range of RNAs, viral RNAs are protected from its endonuclease activity through their assembly into vRNP complexes. These findings provide critical insights into the PA-X-mediated shutoff strategy, revealing how PA-X modulates the cellular environment while sparing the viral genome to favor viral replication.
Keywords: CP: microbiology; PA-X; endonuclease inhibitor; influenza; shutoff.