Ectromelia virus encodes a family of Ankyrin/F-box proteins that regulate NFκB

A notable feature of poxviruses is their ability to inhibit the antiviral response, including the nuclear factor kappa B (NF kappa B) pathway. NF kappa B is a transcription factor that is sequestered in the cytoplasm until cell stimulation, and relies on the SCF (Skp1, culllin-1, F-box) ubiquitin ligase to target its inhibitor, I kappa B alpha, for degradation. I kappa B alpha is recruited to the SCF by the F-box domain-containing protein beta TrCP. Here, we show that ectromelia virus, the causative agent of mousepox, encodes four F-box-containing proteins, EVM002, EVM005, EVM154, and EVM165, all of which contain Ankyrin (Ank) domains. The Ank/F-box proteins inhibit NF kappa B nuclear translocation, and this inhibition is dependent on the F-box domain. We also demonstrate that EVM002, EVM005, EVM154, and EVM165 prevent I kappa B alpha degradation, suggesting that they target the SCF. This study identifies a new mechanism by which ectromelia virus inhibits NF kappa B. (C) 2014 Elsevier Inc. All rights reserved.