Journal
JOURNAL OF VIROLOGY
Volume 88, Issue 9, Pages 4853-4865Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.02923-13
Keywords
-
Categories
Funding
- Canadian Institute of Health Research
- Alberta Innovates-Health Solutions
- Queen Elizabeth II Scholarship
- National Institute of Allergy and Infectious Diseases/National Institutes of Health [A1055530]
Ask authors/readers for more resources
The NF-kappa B signaling pathway plays a critical role in inflammation and innate immunity. Consequently, many viruses have evolved strategies to inhibit NF-kappa B in order to facilitate replication and evasion of the host immune response. Recently, we determined that ectromelia virus, the causative agent of mousepox, contains a family of four BTB/kelch proteins that interact with cullin-3-based ubiquitin ligases. We demonstrate here that expression of EVM150, one of the four BTB/kelch proteins, inhibited NF-kappa B activation induced by tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). Although EVM150 inhibited NF-kappa B p65 nuclear translocation, I kappa B alpha degradation was observed, indicating that EVM150 functioned downstream of I kappa B alpha degradation. Significantly, expression of the BTB-only domain of EVM150 blocked NF-kappa B activation, demonstrating that EVM150 functioned independently of the kelch domain and its role as an adapter for cullin-3-based ubiquitin ligases. Furthermore, cullin-3 knockdown by small interfering RNA demonstrated that cullin-3-based ubiquitin ligases are dispensable for TNF-alpha-induced NF-kappa B activation. Interestingly, nuclear translocation of IRF3 and STAT1 still occurred in the presence of EVM150, indicating that EVM150 prevented NF-kappa B nuclear translocation specifically. In addition to identifying EVM150 as an inhibitor of the NF-kappa B pathway, this study provides new insights into the role of BTB/kelch proteins during virus infection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available