Unknown

Dataset Information

0

ORF3a of SARS-CoV-2 promotes lysosomal exocytosis-mediated viral egress.


ABSTRACT: Viral entry and egress are important determinants of virus infectivity and pathogenicity. β-coronaviruses, including the COVID-19 virus SARS-CoV-2 and mouse hepatitis virus (MHV), exploit the lysosomal exocytosis pathway for egress. Here, we show that SARS-CoV-2 ORF3a, but not SARS-CoV ORF3a, promotes lysosomal exocytosis. SARS-CoV-2 ORF3a facilitates lysosomal targeting of the BORC-ARL8b complex, which mediates trafficking of lysosomes to the vicinity of the plasma membrane, and exocytosis-related SNARE proteins. The Ca2+ channel TRPML3 is required for SARS-CoV-2 ORF3a-mediated lysosomal exocytosis. Expression of SARS-CoV-2 ORF3a greatly elevates extracellular viral release in cells infected with the coronavirus MHV-A59, which itself lacks ORF3a. In SARS-CoV-2 ORF3a, Ser171 and Trp193 are critical for promoting lysosomal exocytosis and blocking autophagy. When these residues are introduced into SARS-CoV ORF3a, it acquires the ability to promote lysosomal exocytosis and inhibit autophagy. Our results reveal a mechanism by which SARS-CoV-2 interacts with host factors to promote its extracellular egress.

SUBMITTER: Chen D 

PROVIDER: S-EPMC8502680 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| EMPIAR-10441 | biostudies-other
| EMPIAR-10439 | biostudies-other
| S-EPMC7205519 | biostudies-literature
| EMPIAR-10612 | biostudies-other
2023-08-29 | GSE224290 | GEO
| EMPIAR-10440 | biostudies-other
| S-SCDT-10_15252-EMBR_202357224 | biostudies-other
| S-EPMC3173716 | biostudies-literature
| S-EPMC5077215 | biostudies-literature
| S-EPMC6650616 | biostudies-literature