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Mutations in modified virus Ankara protein 183 render it a non-functional counterpart of B14, an inhibitor of nuclear

Laura E McCoy1, Aodhnait S Fahy, Ron A-J Chen

  • 1Department of Virology, Imperial College London, London W2 1PG, UK.

The Journal of General Virology
|May 7, 2010
PubMed

Insights

Modified Vaccinia Ankara (MVA) protein 183 is unstable and does not inhibit NF-kappaB activation, unlike its Vaccinia virus counterpart B14. This suggests MVA

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Vaccinia virus (VACV) utilizes proteins like B14 to counteract host innate immunity by inhibiting nuclear factor kappaB (NF-kappaB) activation.
  • Modified Vaccinia Ankara (MVA), an attenuated VACV strain, is a promising vaccine vector, but its immunogenicity may be enhanced by modifying its proteins.

Purpose of the Study:

  • To characterize MVA protein 183, the counterpart of VACV B14, and assess its function in modulating host immune responses.
  • To determine if protein 183 can inhibit NF-kappaB activation and restore virulence in VACV.

Main Methods:

  • Protein stability assays in eukaryotic cells.
  • Assessment of NF-kappaB activation in response to cytokine stimulation.
  • Virulence restoration assays in VACV strains lacking the B14R gene.

Main Results:

  • MVA protein 183 exhibited instability in eukaryotic cells, requiring proteasome inhibition for stability.
  • Protein 183 failed to inhibit NF-kappaB activation.
  • Protein 183 did not restore virulence to VACV lacking the B14R gene.
  • A 6 amino acid deletion in alpha-helix 6 of protein 183 likely explains its instability and lack of function.

Conclusions:

  • MVA protein 183 is functionally distinct from VACV B14 due to instability and inability to inhibit NF-kappaB.
  • The structural difference, specifically the deletion in alpha-helix 6, underlies the functional deficiency of MVA protein 183.
  • These findings provide insights into MVA's immunomodulatory mechanisms and potential for vaccine vector development.

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