Skip to Content
Merck
  • ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-mediated assembly of the SNARE complex required for autolysosome formation.

ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-mediated assembly of the SNARE complex required for autolysosome formation.

Developmental cell (2021-01-11)
Guangyan Miao, Hongyu Zhao, Yan Li, Mingming Ji, Yong Chen, Yi Shi, Yuhai Bi, Peihui Wang, Hong Zhang
ABSTRACT

Autophagy acts as a cellular surveillance mechanism to combat invading pathogens. Viruses have evolved various strategies to block autophagy and even subvert it for their replication and release. Here, we demonstrated that ORF3a of the COVID-19 virus SARS-CoV-2 inhibits autophagy activity by blocking fusion of autophagosomes/amphisomes with lysosomes. The late endosome-localized ORF3a directly interacts with and sequestrates the homotypic fusion and protein sorting (HOPS) component VPS39, thereby preventing HOPS complex from interacting with the autophagosomal SNARE protein STX17. This blocks assembly of the STX17-SNAP29-VAMP8 SNARE complex, which mediates autophagosome/amphisome fusion with lysosomes. Expression of ORF3a also damages lysosomes and impairs their function. SARS-CoV-2 virus infection blocks autophagy, resulting in accumulation of autophagosomes/amphisomes, and causes late endosomal sequestration of VPS39. Surprisingly, ORF3a from the SARS virus SARS-CoV fails to interact with HOPS or block autophagy. Our study reveals a mechanism by which SARS-CoV-2 evades lysosomal destruction and provides insights for developing new strategies to treat COVID-19.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
Pricing and availability is not currently available.
Sigma-Aldrich
Monoclonal Anti-c-Myc antibody produced in mouse, clone 9E10, ascites fluid
Pricing and availability is not currently available.
Sigma-Aldrich
ANTI-STX17 (N-TERM) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Pricing and availability is not currently available.
Roche
Anti-GFP, from mouse IgG1κ (clones 7.1 and 13.1)
Pricing and availability is not currently available.