1887

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Volume 103, Issue 10

Vaccinia virus BTB-Kelch proteins C2 and F3 inhibit NF-κB activation Open Access

Abstract

Vaccinia virus (VACV) encodes scores of proteins that suppress host innate immunity and many of these target intracellular signalling pathways leading to activation of inflammation. The transcription factor NF-κB plays a critical role in the host response to infection and is targeted by many viruses, including VACV that encodes 12 NF-κB inhibitors that interfere at different stages in this signalling pathway. Here we report that VACV proteins C2 and F3 are additional inhibitors of this pathway. C2 and F3 are BTB-Kelch proteins that are expressed early during infection, are non-essential for virus replication, but affect the outcome of infection . Using reporter gene assays, RT-qPCR analyses of endogenous gene expression, and ELISA, these BTB-Kelch proteins are shown here to diminish NF-κB activation by reducing translocation of p65 into the nucleus. C2 and F3 are the 13 and 14 NF-κB inhibitors encoded by VACV. Remarkably, in every case tested, these individual proteins affect virulence and therefore have non-redundant functions. Lastly, immunisation with a VACV strain lacking C2 induced a stronger CD8 T cell response and better protection against virus challenge.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): BTB-Kelch , CD8+ T cell , immune evasion , NF-κB signalling , vaccination and vaccinia virus
Funding
This study was supported by the:
  • Wellcome Trust (Award 090315)
    • Principle Award Recipient: SmithGeoffrey L.
© 2022 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-10-27
2024-05-04
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Vaccinia virus BTB-Kelch proteins C2 and F3 inhibit NF-κB activation
J. Gen. Virol. 103, 001786 (2022); https://doi.org/10.1099/jgv.0.001786
/content/journal/jgv/10.1099/jgv.0.001786
/content/journal/jgv/10.1099/jgv.0.001786
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