Macroautophagy delivers cytoplasmic constituents to lysosomes for degradation. However, the machinery that mediates autophagosome formation and their degradation, participates also in other membrane trafficking events, including endo- and exocytosis. Among these, phagocytosis associated with the autophagosome marker LC3 (LAP) contributes to antigen presentation on MHC class II molecules for helper CD4+ T cell stimulation. During LAP, reactive oxygen species (ROS) produced by NADPH oxidase 2 (NOX2) stabilize LAPosomes in human macrophages by inhibiting LC3 deconjugation from their cytosolic surface. Oxidation-mediated inhibition of the LC3B-deconjugating ATG4B protease sustains MHC class II presentation of exogenous fungal antigens. Redox regulation of ATG4B is therefore an important mechanism for maintaining LC3 decoration of LAPosomes to support antigen processing for MHC class II presentation.
In contrast to this immunity promoting function of the macroautophagy machinery, viruses use parts of it for cytosolic replication compartments and envelope acquisition during non-lytic release. Along these lines, several components of the macroautophagy machinery can be found in purified particles of the human oncogenic Epstein Barr virus (EBV). A viral capsid scaffolding protein that is also contained in purified EBV particles was found to bind to both LC3B, preferentially in its lipidated form, and a viral glycoprotein of the EBV envelope. Accordingly, even in the absence of an essential function of this EBV capsid scaffolding protein for infectious virus production, viral glycoprotein containing membranes were released. These findings suggest a role for LC3B binding to an EBV capsid scaffolding protein in the assembly and release of EBV envelope-like membranes.
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