title: Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes.
abstract: Influenza A virus is an important human pathogen causing significant morbidity and mortality every year and threatening the human population with epidemics and pandemics. Therefore, it is important to understand the biology of this virus to develop strategies to control its pathogenicity. Here, we demonstrate that influenza A virus inhibits macroautophagy, a cellular process known to be manipulated by diverse pathogens. Influenza A virus infection causes accumulation of autophagosomes by blocking their fusion with lysosomes, and one viral protein, matrix protein 2, is necessary and sufficient for this inhibition of autophagosome degradation. Macroautophagy inhibition by matrix protein 2 compromises survival of influenza virus-infected cells but does not influence viral replication. We propose that influenza A virus, which also encodes proapoptotic proteins, is able to determine the death of its host cell by inducing apoptosis and also by blocking macroautophagy.
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University Hospital of Zürich, 8057 Zürich, Switzerland.
authors.forename: Monique
authors.initials: M
authors.lastname: Gannagé
authors.forename: Dorothee
authors.initials: D
authors.lastname: Dormann
authors.forename: Randy
authors.initials: R
authors.lastname: Albrecht
authors.forename: Jörn
authors.initials: J
authors.lastname: Dengjel
authors.forename: Tania
authors.initials: T
authors.lastname: Torossi
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Rämer
authors.forename: Monica
authors.initials: M
authors.lastname: Lee
authors.forename: Till
authors.initials: T
authors.lastname: Strowig
authors.forename: Frida
authors.initials: F
authors.lastname: Arrey
authors.forename: Gina
authors.initials: G
authors.lastname: Conenello
authors.forename: Marc
authors.initials: M
authors.lastname: Pypaert
authors.forename: Jens
authors.initials: J
authors.lastname: Andersen
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002460:Cell Line; D004285:Dogs; D004847:Epithelial Cells / Q000821:virology; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity*; D008247:Lysosomes / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D010588:Phagosomes / Q000378:metabolism* / Q000648:ultrastructure; D014763:Viral Matrix Proteins / Q000502:physiology*; D037521:Virulence Factors / Q000502:physiology*; D000086082:Viroporin Proteins
chemical_list: D014763:Viral Matrix Proteins; D037521:Virulence Factors; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins