PropertyValue
?:abstract
  • SARS-CoV-2 is the causative agent for the COVID-19 pandemic and there is an urgent need to understand the cellular response to SARS-CoV-2 infection. Beclin-1 is an essential scaffold autophagy protein that forms two distinct subcomplexes with modulators Atg14 and UVRAG, responsible for autophagosome formation and maturation, respectively. In the present study, we found that SARS-CoV-2 infection triggers an incomplete autophagy response, elevated autophagosome formation but impaired autophagosome maturation, and declined autophagy by genetic knockout of essential autophagic genes reduces SARS-CoV-2 replication efficiency. By screening 28 viral proteins of SARS-CoV-2, we demonstrated that expression of ORF3a alone is sufficient to induce incomplete autophagy. Mechanistically, SARS-CoV-2 ORF3a interacts with autophagy regulator UVRAG to facilitate Beclin-1-Vps34-Atg14 complex but selectively inhibit Beclin-1-Vps34-UVRAG complex. Interestingly, although SARS-CoV ORF3a shares 72.7% amino acid identity with the SARS-CoV-2 ORF3a, the former had no effect on cellular autophagy response. Thus, our findings provide the mechanistic evidence of possible takeover of host autophagy machinery by ORF3a to facilitate SARS-CoV-2 replication and raises the possibility of targeting the autophagic pathway for the treatment of COVID-19.
is ?:annotates of
?:creator
?:doi
?:doi
  • 10.1101/2020.11.12.380709
?:externalLink
?:journal
  • bioRxiv
?:license
  • biorxiv
?:pdf_json_files
  • document_parses/pdf_json/a411fa25a6389604490642197d8c36795199efd6.json
?:publication_isRelatedTo_Disease
?:sha_id
?:source
  • BioRxiv; WHO
?:title
  • ORF3a mediated-incomplete autophagy facilitates SARS-CoV-2 replication
?:type
?:year
  • 2020-11-12

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