Marburg virus regulates the IRE1/XBP1-dependent unfolded protein response to ensure efficient viral replication

Area of Science:

• Virology
• Cellular Biology
• Molecular Biology

Background:

• Viruses manipulate host cell signaling for replication.
• Marburg virus (MARV) infection can trigger the unfolded protein response (UPR) via ER stress.
• The IRE1-XBP1 pathway is a key UPR signaling axis.

Purpose of the Study:

• To investigate the role of the IRE1-XBP1 UPR pathway during MARV infection.
• To identify MARV proteins involved in regulating UPR.
• To understand how MARV modulates cellular signaling for replication.

Main Methods:

• UPRE luciferase assays to monitor UPR activation.
• Western blotting to detect IRE1 phosphorylation and XBP1 splicing.
• Co-expression and co-immunoprecipitation studies of MARV proteins.
• IRE1 knock-out experiments.

Main Results:

• Ectopic MARV glycoprotein (GP) expression activated the IRE1-XBP1 axis.
• MARV infection showed transient IRE1 phosphorylation but limited XBP1s expression and no UPRE activity at later time points.
• MARV protein VP30 suppressed UPR activation and interacted with XBP1u in an RNA-dependent manner.
• IRE1 knock-out enhanced MARV infection at late stages.

Conclusions:

• MARV efficiently propagates by specifically regulating the IRE1-XBP1 UPR pathway.
• The MARV protein VP30 plays a critical role in suppressing UPR, facilitating viral replication.
• Understanding MARV's interaction with host UPR is key to developing antiviral strategies.