title: A LC3-interacting motif in the influenza A virus M2 protein is required to subvert autophagy and maintain virion stability.
abstract: Autophagy recycles cellular components and defends cells against intracellular pathogens. While viruses must evade autophagocytic destruction, some viruses can also subvert autophagy for their own benefit. The ability of influenza A virus (IAV) to evade autophagy depends on the Matrix 2 (M2) ion-channel protein. We show that the cytoplasmic tail of IAV M2 interacts directly with the essential autophagy protein LC3 and promotes LC3 relocalization to the unexpected destination of the plasma membrane. LC3 binding is mediated by a highly conserved LC3-interacting region (LIR) in M2. The M2 LIR is required for LC3 redistribution to the plasma membrane in virus-infected cells. Mutations in M2 that abolish LC3 binding interfere with filamentous budding and reduce virion stability. IAV therefore subverts autophagy by mimicking a host short linear protein-protein interaction motif. This strategy may facilitate transmission of infection between organisms by enhancing the stability of viral progeny.
authors: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; University of Cambridge, Department of Medicine, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors: Rupert
authors: R
authors: Beale
authors: Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, UK; Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 0QQ, UK.
authors: Helen
authors: H
authors: Wise
authors: Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 0QQ, UK.
authors: Amanda
authors: A
authors: Stuart
authors: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors: Benjamin J
authors: BJ
authors: Ravenhill
authors: Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, UK; Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 0QQ, UK. Electronic address: paul.digard@roslin.ed.ac.uk.
authors: Paul
authors: P
authors: Digard
authors: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; University of Cambridge, Department of Medicine, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Electronic address: randow@mrc-lmb.cam.ac.uk.
authors: Felix
authors: F
authors: Randow
mesh_terms: D001343:Autophagy; D054884:Host-Pathogen Interactions; D009980:Influenza A virus / Q000235:genetics / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000502:physiology*; D000086082:Viroporin Proteins
chemical_list: D008869:Microtubule-Associated Proteins; D050505:Mutant Proteins; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C477012:MAP1LC3A protein, human