ORF3a of SARS-CoV-2 promotes lysosomal exocytosis-mediated viral egress.
Dev Cell
; 56(23): 3250-3263.e5, 2021 12 06.
Artículo
en Inglés
| MEDLINE | ID: covidwho-1458566
ABSTRACT
Viral entry and egress are important determinants of virus infectivity and pathogenicity. ß-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.
Palabras clave
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Autofagia
/
Factores de Ribosilacion-ADP
/
Canales de Potencial de Receptor Transitorio
/
Exocitosis
/
Liberación del Virus
/
Proteínas Viroporinas
/
Lisosomas
Límite:
Animales
/
Humanos
Idioma:
Inglés
Revista:
Dev Cell
Asunto de la revista:
Embriología
Año:
2021
Tipo del documento:
Artículo
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