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

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

Author information

1
Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, 6-020 Katz Group Center, Edmonton, Alberta, Canada, T6G 2E1. Electronic address: burles@ualberta.ca.
2
Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, 6-020 Katz Group Center, Edmonton, Alberta, Canada, T6G 2E1.

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

PMID:
25240225
DOI:
10.1016/j.virol.2014.08.030
[Indexed for MEDLINE]
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