Mutations in modified virus Ankara protein 183 render it a non-functional counterpart of B14, an inhibitor of nuclear factor kappaB activation.
Vaccinia virus (VACV) encodes multiple proteins to evade host innate immunity, including B14, a virulence factor that binds to the inhibitor of kappaB kinase beta (IKKbeta) and blocks nuclear factor kappaB (NF-kappaB) activation. B14 shares 95 % amino acid identity with the 183 protein encoded by modified virus Ankara (MVA), an attenuated VACV strain being developed as a vaccine vector. To evaluate whether the immunogenicity of MVA might be increased by manipulation of MVA immunomodulatory proteins, the MVA counterpart of B14, protein 183, was characterized. Unlike B14, protein 183 was unstable in eukaryotic cells unless proteasome-mediated protein degradation was inhibited. Furthermore, 183 did not inhibit NF-kappaB activation in response to cytokine stimulation, and did not restore the virulence of VACV strain Western Reserve lacking gene B14R. The instability and non-functionality of 183 are probably explained by a deletion of 6 aa within alpha-helix 6 of the B14 crystal structure.
McCoy
Laura E
LE
Department of Virology, Imperial College London, London W2 1PG, UK.
Fahy
Aodhnait S
AS
Chen
Ron A-J
RA
Smith
Geoffrey L
GL
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D005814:Genes, Viral; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology; D014774:Virulence / Q000235:genetics / Q000276:immunology
D050505:Mutant Proteins; D016328:NF-kappa B; D014764:Viral Proteins; D014765:Viral Vaccines
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