Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes.
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.
Gannagé
Monique
M
Viral Immunobiology, Institute of Experimental Immunology, University Hospital of Zürich, 8057 Zürich, Switzerland.
Dormann
Dorothee
D
Albrecht
Randy
R
Dengjel
Jörn
J
Torossi
Tania
T
Rämer
Patrick C
PC
Lee
Monica
M
Strowig
Till
T
Arrey
Frida
F
Conenello
Gina
G
Pypaert
Marc
M
Andersen
Jens
J
García-Sastre
Adolfo
A
Münz
Christian
C
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
D014763:Viral Matrix Proteins; D037521:Virulence Factors; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins