Ebola Virus Activates IRE1α-Dependent XBP1u Splicing

Area of Science:

• Virology
• Cellular Biology
• Molecular Biology

Background:

• Ebola virus (EBOV) and Marburg virus (MARV) are pathogenic filoviruses impacting host cell signaling.
• MARV manipulates the IRE1α-dependent unfolded protein response (UPR) for replication.
• The effect of EBOV on this UPR pathway was previously unknown.

Purpose of the Study:

• To investigate whether EBOV infection influences the IRE1α-dependent UPR signaling pathway.
• To compare EBOV's UPR manipulation strategy with that of MARV.
• To identify viral factors responsible for UPR activation by EBOV.

Main Methods:

• Assessing UPR activation markers (IRE1α, XBP1s, UPRE target genes) in EBOV-infected cells.
• Evaluating the roles of EBOV nucleoprotein (NP) and soluble glycoprotein (sGP) in UPR activation.
• Testing the impact of UPR activation/inhibition on EBOV and MARV replication using thapsigargin and XBP1 knock-out.

Main Results:

• EBOV infection activated IRE1α-dependent UPR signaling, but not ATF6-dependent signaling.
• UPR activation in EBOV infection was linked to the viral NP and sGP proteins.
• Unlike MARV, EBOV replication was unaffected by UPR modulation (thapsigargin treatment or XBP1 knock-out).

Conclusions:

• EBOV and MARV exhibit divergent strategies in utilizing the IRE1α-dependent UPR pathway.
• EBOV activates UPR but does not rely on it for replication, suggesting a non-essential role or a different functional outcome.
• MARV's replication is dependent on UPR activation, highlighting a critical role for this pathway in its life cycle.