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

Virology. 2014 Nov;468-470:351-362. doi: 10.1016/j.virol.2014.08.030. Epub 2014 Sep 18.

Abstract

A notable feature of poxviruses is their ability to inhibit the antiviral response, including the nuclear factor kappa B (NFκB) pathway. NFκB 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, IκBα, for degradation. IκBα is recruited to the SCF by the F-box domain-containing protein βTrCP. 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 NFκB nuclear translocation, and this inhibition is dependent on the F-box domain. We also demonstrate that EVM002, EVM005, EVM154, and EVM165 prevent IκBα degradation, suggesting that they target the SCF. This study identifies a new mechanism by which ectromelia virus inhibits NFκB.

Keywords: Ankyrin; EVM002; EVM005; EVM154; EVM165; Ectromelia virus; F-box; NFκB; Poxvirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Ankyrins / genetics
  • Ankyrins / metabolism*
  • Cell Line
  • Ectromelia virus / genetics
  • Ectromelia virus / metabolism*
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism*
  • Gene Expression Regulation, Viral / physiology*
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism
  • Multigene Family
  • NF-kappa B / metabolism*
  • Plasmids
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*

Substances

  • Ankyrins
  • F-Box Proteins
  • NF-kappa B
  • Viral Proteins
  • SKP Cullin F-Box Protein Ligases
  • I-kappa B Kinase