Ectromelia virus encodes an anti-apoptotic protein that regulates cell death

- Here we characterize EVM025 of Ectromelia virus, the orthologue of Vaccinia virus F1L.
- EVM025 is crucial in preventing apoptosis induced by virus infection.
- EVM025 is inhibits the activation of the pro-apoptotic protein Bak and Bax.
- EVM025 inhibits Bak by direct interaction, and Bax by sequestering the BH3-only Bim.
- Provides a detail characterization of EVM025 in an in-vivo system.

Apoptosis serves as a powerful defense against damaged or pathogen-infected cells. Since apoptosis is an effective defense against viral infection, many viruses including poxviruses, encode proteins to prevent or delay apoptosis. Here we show that ectromelia virus, the causative agent of mousepox encodes an anti-apoptotic protein EVM025. Here we demonstrate that expression of functional EVM025 is crucial to prevent apoptosis triggered by virus infection and staurosporine. We demonstrate that the expression of EVM025 prevents the conformational activation of the pro-apoptotic proteins Bak and Bax, allowing the maintenance of mitochondrial membrane integrity upon infection with ECTV. Additionally, EVM025 interacted with intracellular Bak. We were able to demonstrate that EVM025 ability to inhibit Bax activation is a function of its ability to inhibit the activity of an upstream BH3 only protein Bim. Collectively, our data indicates that EVM025 inhibits apoptosis by sequestering Bak and inhibiting the activity of Bak and Bax.