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ORF3a of SARS-CoV-2 blocks fusion between autophagosomes/amphisomes and endolysosomes
SARS-CoV-2’s ORF3a localizes to late endosomes and lysosomes, where it binds to VPS39 of the HOPS complex. The resulting HOPS complex is unable to mediate STX17-SNAP29-VAMP8 SNARE complex formation. As this SNARE complex mediates autophagosome-lysosome fusion, autophagosomes or amphisomes (autophagosomes that have fused with late endosomes) are unable to mature to autolysosomes in cells with ORF3a.
