Nondegradative role of Atg5-Atg12/ Atg16L1 autophagy protein complex in antiviral activity of interferon gamma

Cell Host Microbe. 2012 Apr 19;11(4):397-409. doi: 10.1016/j.chom.2012.03.002.


Host resistance to viral infection requires type I (α/β) and II (γ) interferon (IFN) production. Another important defense mechanism is the degradative activity of macroautophagy (herein autophagy), mediated by the coordinated action of evolutionarily conserved autophagy proteins (Atg). We show that the Atg5-Atg12/Atg16L1 protein complex, whose prior known function is in autophagosome formation, is required for IFNγ-mediated host defense against murine norovirus (MNV) infection. Importantly, the direct antiviral activity of IFNγ against MNV in macrophages required Atg5-Atg12, Atg7, and Atg16L1, but not induction of autophagy, the degradative activity of lysosomal proteases, fusion of autophagosomes and lysosomes, or the Atg8-processing protein Atg4B. IFNγ, via Atg5-Atg12/Atg16L1, inhibited formation of the membranous cytoplasmic MNV replication complex, where Atg16L1 localized. Thus, the Atg5-Atg12/Atg16L1 complex performs a pivotal, nondegradative role in IFNγ-mediated antiviral defense, establishing that multicellular organisms have evolved to use portions of the autophagy pathway machinery in a cassette-like fashion for host defense.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Autophagy-Related Protein 12
  • Autophagy-Related Protein 5
  • Autophagy-Related Proteins
  • Caliciviridae Infections / genetics
  • Caliciviridae Infections / immunology
  • Caliciviridae Infections / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Humans
  • Interferon-gamma / immunology*
  • Mice
  • Mice, Knockout
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Norovirus / physiology*
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism*


  • Atg12 protein, mouse
  • Atg16l1 protein, mouse
  • Atg5 protein, mouse
  • Autophagy-Related Protein 12
  • Autophagy-Related Protein 5
  • Autophagy-Related Proteins
  • Carrier Proteins
  • Microtubule-Associated Proteins
  • Proteins
  • Interferon-gamma