The novel ORFV protein ORFV113 activates LPA-p38 signaling

Area of Science:

• Virology
• Cellular Signaling
• Immunology

Background:

• Viruses manipulate host cell pathways for replication.
• G protein-coupled receptors (GPCRs) regulate cellular functions.
• p38 kinase is crucial for innate immunity and cell responses.

Purpose of the Study:

• To identify and characterize novel viral proteins that modulate host signaling.
• To investigate the role of ORFV113 in viral pathogenesis and host immune response.

Main Methods:

• Protein-protein interaction assays to identify ORFV113 target.
• In vitro and in vivo experiments to assess p38 kinase phosphorylation.
• Viral infection models in cell cultures and sheep.
• Gene knockdown and pharmacological inhibition of LPA1 and p38 pathways.

Main Results:

• ORFV113 directly interacts with Lysophosphatidic acid receptor 1 (LPA1).
• ORFV113 enhances p38 kinase phosphorylation, crucial for viral replication and virulence.
• Deletion of ORFV113 attenuates virus replication and reduces disease severity in sheep.
• Targeting LPA1 or p38 signaling inhibits viral propagation.

Conclusions:

• ORFV113 is a key viral virulence factor that exploits the LPA1-p38 signaling axis.
• This study reveals a novel mechanism of viral immune evasion via GPCR modulation.
• ORFV113 is the first identified viral protein targeting p38 signaling through LPA1.