The equine arteritis virus induces apoptosis via caspase-8 and mitochondria-dependent caspase-9 activation

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Equine arteritis virus (EAV), an arterivirus, is known to induce apoptosis in vitro.
• Understanding the specific molecular pathways of apoptosis induction is crucial for viral pathogenesis research.

Purpose of the Study:

• To elucidate the caspase activation pathways involved in EAV-induced apoptosis.
• To investigate the roles of caspase-8 and caspase-9 in the apoptotic process triggered by EAV.

Main Methods:

• Treatment of target cells with specific peptide inhibitors of caspases (Z-VAD-FMK, Z-IETD-FMK, Z-LEHD-FMK) prior to EAV infection.
• Analysis of apoptosis inhibition in cells expressing apoptosis-modulating proteins (HSV2-R1, hsp70).
• Assessment of Bid activation and cytochrome c translocation.

Main Results:

• All tested peptide inhibitors significantly inhibited EAV-induced apoptosis.
• Apoptosis was also inhibited in cells expressing proteins known to modulate caspase-8 and caspase-9 activation pathways.
• Evidence of Bid activation and cytochrome c translocation confirmed the involvement of these signaling molecules.

Conclusions:

• Equine arteritis virus induces apoptosis via a pathway initiated by caspase-8 activation.
• This is followed by mitochondria-dependent activation of caspase-9.
• The findings provide a detailed understanding of the molecular mechanisms underlying EAV-induced cell death.