Multiple Bcl-2 family immunomodulators from vaccinia virus regulate MAPK/AP-1 activation

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Vaccinia virus (VACV) modulates host cell metabolism and immune responses.
• VACV infection activates the mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) pathway.
• VACV inhibits the pro-inflammatory transcription factor NF-κB pathway.

Purpose of the Study:

• To investigate if VACV Bcl-2-like NF-κB inhibitors influence MAPK/AP-1 activation.
• To identify specific VACV proteins involved in AP-1 activation.

Main Methods:

• Expression of six different VACV Bcl-2-like NF-κB inhibitors.
• Analysis of AP-1 activation during VACV infection and individual protein expression.
• Investigation of MAPK pathway activation (ERK, JNK) and c-Jun phosphorylation.

Main Results:

• Proteins A52, B14, and K7 contribute to AP-1 activation during VACV infection.
• Individual expression of A52, B14, and K7 also leads to AP-1 activation.
• Protein B14 demonstrated the strongest AP-1 stimulation, primarily activating ERK and JNK MAPKs and their substrate c-Jun.

Conclusions:

• The same viral protein can exert opposing effects on distinct signaling pathways.
• VACV proteins can simultaneously inhibit NF-κB activation and promote MAPK/AP-1 activation.