tetano
Editor, Senior Moderator
EMBO Rep
. 2025 Mar 3.
doi: 10.1038/s44319-025-00388-7. Online ahead of print. Caspase cleavage of influenza A virus M2 disrupts M2-LC3 interaction and regulates virion production
Carmen Figueras-Novoa[SUP] 1 2 [/SUP], Masato Akutsu[SUP] #[/SUP][SUP] 3 4 [/SUP], Daichi Murata[SUP] #[/SUP][SUP] 3 5 6 [/SUP], Anne Weston[SUP] 7 [/SUP], Ming Jiang[SUP] 8 [/SUP], Beatriz Montaner[SUP] 1 [/SUP], Christelle Dubois[SUP] 9 [/SUP], Avinash Shenoy[SUP] 10 11 [/SUP], Rupert Beale[SUP] 12 13 [/SUP]
Affiliations
Influenza A virus (IAV) Matrix 2 protein (M2) is an ion channel, required for efficient viral entry and egress. M2 interacts with the small ubiquitin-like LC3 protein through a cytoplasmic C-terminal LC3-interacting region (LIR). Here, we report that M2 is cleaved by caspases, abolishing the M2-LC3 interaction. A crystal structure of the M2 LIR in complex with LC3 indicates the caspase cleavage tetrapeptide motif ([SUB]82[/SUB]SAVD[SUB]85[/SUB]) is an unstructured linear motif that does not overlap with the LIR. IAV mutant expressing a permanently truncated M2, mimicking caspase cleavage, exhibit defects in M2 plasma membrane transport, viral filament formation, and virion production. Our results reveal a dynamic regulation of the M2-LC3 interaction by caspases. This highlights the role of host proteases in regulating IAV exit, relating virion production with host cell state.
Keywords: Autophagy; Caspase; Influenza; LC3; M2.
. 2025 Mar 3.
doi: 10.1038/s44319-025-00388-7. Online ahead of print. Caspase cleavage of influenza A virus M2 disrupts M2-LC3 interaction and regulates virion production
Carmen Figueras-Novoa[SUP] 1 2 [/SUP], Masato Akutsu[SUP] #[/SUP][SUP] 3 4 [/SUP], Daichi Murata[SUP] #[/SUP][SUP] 3 5 6 [/SUP], Anne Weston[SUP] 7 [/SUP], Ming Jiang[SUP] 8 [/SUP], Beatriz Montaner[SUP] 1 [/SUP], Christelle Dubois[SUP] 9 [/SUP], Avinash Shenoy[SUP] 10 11 [/SUP], Rupert Beale[SUP] 12 13 [/SUP]
Affiliations
- PMID: 40033051
- DOI: 10.1038/s44319-025-00388-7
Influenza A virus (IAV) Matrix 2 protein (M2) is an ion channel, required for efficient viral entry and egress. M2 interacts with the small ubiquitin-like LC3 protein through a cytoplasmic C-terminal LC3-interacting region (LIR). Here, we report that M2 is cleaved by caspases, abolishing the M2-LC3 interaction. A crystal structure of the M2 LIR in complex with LC3 indicates the caspase cleavage tetrapeptide motif ([SUB]82[/SUB]SAVD[SUB]85[/SUB]) is an unstructured linear motif that does not overlap with the LIR. IAV mutant expressing a permanently truncated M2, mimicking caspase cleavage, exhibit defects in M2 plasma membrane transport, viral filament formation, and virion production. Our results reveal a dynamic regulation of the M2-LC3 interaction by caspases. This highlights the role of host proteases in regulating IAV exit, relating virion production with host cell state.
Keywords: Autophagy; Caspase; Influenza; LC3; M2.