EVM005: An Ectromelia-Encoded Protein with Dual Roles in NF-κB Inhibition and Virulence

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Poxviruses are large dsDNA viruses that are renowned for regulating cellular pathways and manipulating the host immune response, including the NF-κB pathway. NF-κB inhibition by poxviruses is a growing area of interest and this family of viruses has developed multiple mechanisms to manipulate the pathway. Here, we focus on regulation of the NF-κB pathway by ectromelia virus, the causative agent of mousepox. We demonstrate that ectromelia virus is a potent inhibitor of the NF-κB pathway. Previously, we identified a family of four ectromelia virus genes that contain N-terminal ankyrin repeats and a C-terminal F-box domain that interacts with the cellular SCF ubiquitin ligase. Significantly, expression of the ankyrin/F-box protein, EVM005, inhibited NF-κB, and the F-box domain was critical for NF-κB inhibition and interaction with the SCF complex. Ectromelia virus devoid of EVM005 still inhibited NF-κB, indicating that multiple gene products contribute to NF-κB inhibition. Importantly, mice infected with ectromelia virus lacking EVM005 had a robust immune response, leading to viral clearance during infection. The data present two mechanisms, one in which EVM005 inhibits NF-κB activation through manipulation of the host SCF ubiquitin ligase complex, and an additional, NF-κB-independent mechanism that drives virulence.

Vyšlo v časopise: EVM005: An Ectromelia-Encoded Protein with Dual Roles in NF-κB Inhibition and Virulence. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004326
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004326

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