Related Experiment Video

Updated: Oct 8, 2025

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
10:12

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity

Published on: June 14, 2024

2.2K

SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein Response

Wen-Qing Su1, Xue-Jie Yu1, Chuan-Min Zhou1

  • 1State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan 430071, China.

Viruses
|December 28, 2021
PubMed

Insights

SARS-CoV-2 ORF3a protein induces incomplete autophagy, a cellular process, via the unfolded protein response (UPR) pathways. This discovery offers insights into COVID-19 pathogenesis and potential therapeutic strategies.

Area of Science:

  • Virology
  • Cellular Biology
  • Immunology

Background:

  • SARS-CoV-2 has caused a global health crisis with millions of cases and deaths.
  • Autophagy plays a dual role in viral infections, either promoting or inhibiting them.
  • Coronaviruses exploit autophagy-dependent vesicles, but the induction mechanisms are poorly understood.

Purpose of the Study:

  • To investigate the role of SARS-CoV-2 ORF3a protein in inducing autophagy.
  • To elucidate the specific cellular pathways involved in ORF3a-mediated autophagy induction.

Main Methods:

  • Utilized autophagy-deficient cell lines and autophagy inhibitors.
  • Investigated the involvement of SARS-CoV-2 ORF3a in autophagy and unfolded protein response (UPR).
  • Examined the roles of IRE1, ATF6, and PERK pathways in ORF3a-induced autophagy.

Main Results:

  • SARS-CoV-2 ORF3a induced incomplete autophagy in a FIP200/Beclin-1-dependent manner.
  • ORF3a triggered the unfolded protein response (UPR).
  • The IRE1 and ATF6 UPR pathways, but not PERK, mediated ORF3a-induced autophagy.

Conclusions:

  • The UPR pathway is crucial for ORF3a-induced classical autophagy.
  • Understanding this mechanism enhances comprehension of SARS-CoV-2 infection.
  • Identified potential therapeutic targets for COVID-19 treatment.
Keywords:
ORF3aSARS-CoV-2UPRautophagycoronavirus

More Related Videos

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells09:10

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells

Published on: October 28, 2019

7.4K
Study of Protein-protein Interactions in Autophagy Research14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

9.3K

Related Concept Videos

The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
5.2K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.7K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.8K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.6K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.1K
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
8.1K