A LC3-Interacting Motif in the Influenza A Virus M2 Protein Is Required to Subvert Autophagy and Maintain Virion Stability

Rupert Beale, Helen Wise, Amanda Stuart, Benjamin J. Ravenhill, Paul Digard, and Felix Randow. Cell Host Microbe (2014) 15, 239–247

Speaker: Chieh-Yu Lin (林倢妤)                          Time: 15:00~16:00, Oct. 1, 2014

Commentator: Dr. Ai-Li Shiau (蕭璦莉老師)      Place: Room 601

Abstract:

Autophagy can selectively target intracellular pathogens and has been adapted as a host defense mechanism. The ability of autophagy to defend pathogens depends on cargo proteins, which simultaneously detect pathogen-associated signals and bind to autophagosomal membrane proteins, ATG8/LC3 family. The binding partners of ATG/LC3 family typically contain the LC3-interacting region (LIR). Although viruses must evade autophagocytic destruction, they can also benefit from the resources provided by autophagy. Influenza A virus (IAV) is an important human pathogens which causes seasonal epidemics and sporadic pandemic and can affect host autophagy. IAV affects autophagy through its Matrix 2 (M2) ion-channel protein by blocking fusion ofautophagosomes and lysosomes [1]. To investigate the autophagocytic mechanisms manipulated by IAV during infection, the authors performed fluorescence anisotropy. The results showed that LC3 was distributed to not only perinuclear regions, the common region which LC3 accumulates during autophagy, but also plasma membrane, the unusual destination, in cell infected with IAV. Furthermore, to determine whether IAV M2 protein participates in this process, the authors analyzed the interaction between IAV M2 protein and LC3. The bond with LC3 was mediated by a highly conserved LIR in the cytoplasmic tail of M2 protein, the first such motif discovered in IAV. The M2 LIR was required for the redistribution of LC3 to the plasma membrane of IAV-infected cells. Since M2 protein had been reported to regulate virus budding [2], the authors also investigated the role of autophagocytic mechanism manipulated by M2 in virus life cycle. Mutations in M2 that abolished the LC3 redistribution to plasma membrane further interfered with filamentous budding and reduced virion stability. It was an efficient strategy regulating autophagy through IAV M2 protein that might facilitate the transmission of infection between organisms by enhancing the stability of viral progeny.

References:

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