The ER stress sensor IRE1 and MAP kinase ERK modulate autophagy induction in cells infected with coronavirus infectious bronchitis virus.

Abstract

Coronavirus infection induces the generation of autophagosomes, and certain host proteins regulating cellular autophagy are hijacked by some coronaviruses to facilitate the formation of double membrane vesicles. However, mechanisms underlying coronavirus-induced autophagy remain largely unknown. In this study, we demonstrate that autophagosome formation and apparent autophagic flux are induced in cells infected with infectious bronchitis virus (IBV) - a gammacoronavirus. Notably, IBV-induced autophagy was dependent on autophagy related 5 (ATG5) but not beclin1 (BECN1), although both are essential proteins in the canonical autophagy pathway. Moreover, the ER stress sensor inositol requiring enzyme 1 (IRE1), but not its substrate X-box protein 1 (XBP1), was also essential for the induction of autophagy during IBV infection. Finally, the anti-apoptotic extracellular signal-regulated kinase 1/2 (ERK1/2) also contributed to IBV-induced autophagy. Our findings add new knowledge to the regulatory mechanisms governing coronavirus-induced autophagy, highlighting an extensive cross-talk among cellular signaling pathways during coronavirus infection.

• Authors: To Sing Fung, Ding Xiang Liu
• Journal: Virology (Virology) Vol. 533 Pg. 34-44 (07 2019) ISSN: 1096-0341 [Electronic] United States
• PMID: 31082732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Autophagy-Related Protein 5
• BECN1 protein, human
• Beclin-1
• ERN1 protein, human
• Protein Serine-Threonine Kinases
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Endoribonucleases

Topics

• Autophagy
• Autophagy-Related Protein 5 (genetics, metabolism)
• Beclin-1 (genetics, metabolism)
• Coronavirus Infections (genetics, metabolism, physiopathology, virology)
• Endoplasmic Reticulum Stress
• Endoribonucleases (genetics, metabolism)
• Humans
• Infectious bronchitis virus (genetics, physiology)
• Mitogen-Activated Protein Kinase 1 (genetics, metabolism)
• Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
• Protein Serine-Threonine Kinases (genetics, metabolism)