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Contribution of autophagy machinery factors to HCV and SARS-CoV-2 replication organelle formation.
- Source :
-
Cell reports [Cell Rep] 2021 Nov 23; Vol. 37 (8), pp. 110049. Date of Electronic Publication: 2021 Nov 10. - Publication Year :
- 2021
-
Abstract
- Positive-strand RNA viruses replicate in close association with rearranged intracellular membranes. For hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), these rearrangements comprise endoplasmic reticulum (ER)-derived double membrane vesicles (DMVs) serving as RNA replication sites. Cellular factors involved in DMV biogenesis are poorly defined. Here, we show that despite structural similarity of viral DMVs with autophagosomes, conventional macroautophagy is dispensable for HCV and SARS-CoV-2 replication. However, both viruses exploit factors involved in autophagosome formation, most notably class III phosphatidylinositol 3-kinase (PI3K). As revealed with a biosensor, PI3K is activated in cells infected with either virus to produce phosphatidylinositol 3-phosphate (PI3P) while kinase complex inhibition or depletion profoundly reduces replication and viral DMV formation. The PI3P-binding protein DFCP1, recruited to omegasomes in early steps of autophagosome formation, participates in replication and DMV formation of both viruses. These results indicate that phylogenetically unrelated HCV and SARS-CoV-2 exploit similar components of the autophagy machinery to create their replication organelles.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Autophagosomes metabolism
Carrier Proteins metabolism
Class III Phosphatidylinositol 3-Kinases antagonists & inhibitors
Class III Phosphatidylinositol 3-Kinases metabolism
Humans
Phosphatidylinositol Phosphates metabolism
RNA, Viral biosynthesis
Viral Nonstructural Proteins metabolism
Virus Replication
Autophagy physiology
Hepacivirus physiology
SARS-CoV-2 physiology
Viral Replication Compartments metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 37
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 34788596
- Full Text :
- https://doi.org/10.1016/j.celrep.2021.110049