Virus-induced p38 MAPK activation facilitates viral infection

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Viral infections frequently activate the p38 mitogen-activated protein kinase (MAPK) pathway.
• The precise role and mechanisms of p38 activation during viral infections remain incompletely understood.

Purpose of the Study:

• To investigate the role of virus-hijacked p38 MAPK activation in viral replication.
• To elucidate the molecular mechanisms by which p38 activation influences viral processes.
• To evaluate the potential of targeting p38 activation as a broad-spectrum antiviral strategy.

Main Methods:

• Correlation analysis of hepatitis C virus (HCV) infection and p38 activation in patient tissues and primary human hepatocytes (PHHs) using immunohistochemistry and western blotting.
• Investigated p38α and HCV core protein interaction via coimmunoprecipitation, GST pulldown, and confocal microscopy.
• Assessed p38 activation effects on viral replication using plaque assays, qRT-PCR, western blotting, siRNA, and CRISPR/Cas9.

Main Results:

• HCV infection correlated with p38 activation, induced by the interaction of p38α with TAB1, facilitating viral replication.
• Activated p38α phosphorylated the HCV core protein, promoting viral assembly; inhibition with SB203580 suppressed HCV infection.
• p38 MAPK activation was also observed in infections with SFTSV, HSV-1, and SARS-CoV-2, and SB203580 inhibited these viruses.

Conclusions:

• Virus-hijacked p38 activation is a critical determinant of viral replication across multiple virus families.
• Pharmacological inhibition of p38 activation presents a promising and potentially broad-spectrum antiviral therapeutic approach.