Cyclooxygenase-2 Facilitates Newcastle Disease Virus Proliferation and Is as a Target for Canthin-6-One Antiviral...

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Cyclooxygenase-2 (COX-2) is involved in inflammation and antiviral defense.
• The specific role of COX-2 in Newcastle disease virus (NDV) proliferation was previously unclear.

Purpose of the Study:

• To elucidate the role of COX-2 in NDV proliferation.
• To identify regulatory mechanisms of COX-2 during NDV infection.
• To explore COX-2 as a potential therapeutic target against NDV.

Main Methods:

• Investigated NDV proliferation under varying COX-2 expression levels (inhibition and overexpression).
• Analyzed effects on endoplasmic reticulum (ER)-stress, autophagy, and antiviral gene expression.
• Utilized inhibitors and siRNA to identify signaling pathways (NF-κB, MDA5) regulating COX-2.
• Assessed the impact of canthin-6-one analogs on COX-2 expression and NDV proliferation.

Main Results:

• COX-2 inhibition enhanced NDV proliferation; COX-2 overexpression suppressed it dose-dependently.
• Overexpression of COX-2 reduced ER-stress and autophagy, and boosted antiviral gene expression.
• Nuclear factor-κB (NF-κB) and MDA5 were identified as key mediators of NDV-induced COX-2 expression.
• NDV infection led to suppressed COX-2 protein synthesis and reduced mRNA half-life at later stages.
• Canthin-6-one analogs activated COX-2 and inhibited NDV proliferation at the micromolar level.

Conclusions:

• COX-2 is a critical regulator of NDV proliferation, acting through modulation of cellular stress responses and antiviral pathways.
• NDV tightly regulates COX-2 expression, involving NF-κB and MDA5 signaling.
• COX-2 represents a promising therapeutic target for developing anti-NDV agents.