Figure 9.

A possible mechanism by which vaccinia virus disrupts autophagy machinery. (A) The functions of the ATG12 and LC3 ubiquitin-like protein conjugation systems are required for normal autophagosome formation. The ATG12 ubiquitin-like conjugation system leads to formation of the ATG12–ATG5–ATG16L multimeric complex, which serves as an E3-like enzyme for lipidation of LC3 at phagophore, facilitating autophagosome maturation. (B) Vaccinia virus infection causes ATG12–ATG3 conjugation, which may have both E2- and E3-like enzyme activity. The ATG12–ATG3 complex results in massive aberrant LC3 lipidation which is dislocated from phagophore, causing failure in autophagosome formation.