Seneca Valley Virus 3C Protease Inhibits Stress Granule Formation by Disrupting eIF4GI-G3BP1 Interaction

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Stress granules (SGs) are dynamic cytoplasmic foci involved in mRNA regulation during cellular stress and viral infections.
• Seneca Valley virus (SVV), an oncolytic RNA virus, causes vesicular disease in pigs.
• Understanding SVV's interaction with host cell machinery like SGs is crucial for viral pathogenesis research.

Purpose of the Study:

• To investigate the role of stress granules (SGs) during Seneca Valley virus (SVV) infection.
• To elucidate the mechanisms by which SVV induces and regulates SG formation.
• To determine the impact of SG modulation on SVV propagation and host immune responses.

Main Methods:

• SVV infection of cells and observation of SG formation using marker proteins (G3BP1, eIF4GI).
• Manipulation of SG-related proteins (TIA1, G3BP1) and signaling pathways (PKR-eIF2α, NF-κB).
• Enzymatic activity assays of SVV 3C protease and analysis of protein interactions (eIF4GI-G3BP1).

Main Results:

• SVV infection induced transient SG formation in a PKR-eIF2α-dependent manner.
• Inhibition of SG formation did not significantly affect SVV propagation.
• G3BP1 depletion attenuated NF-κB signaling pathway activation.
• SVV 3C protease inhibited SG formation late in infection by disrupting eIF4GI-G3BP1 interaction.

Conclusions:

• SVV induces transient SGs via PKR-eIF2α phosphorylation early in infection.
• SVV 3C protease inhibits SGs late in infection by disrupting eIF4GI-G3BP1 interaction.
• Modulation of SGs impacts host NF-κB signaling but not viral propagation.