1887

Abstract

Vaccinia virus (VACV) encodes multiple proteins to evade host innate immunity, including B14, a virulence factor that binds to the inhibitor of B kinase (IKK) and blocks nuclear factor B (NF-B) 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-B activation in response to cytokine stimulation, and did not restore the virulence of VACV strain Western Reserve lacking gene . The instability and non-functionality of 183 are probably explained by a deletion of 6 aa within -helix 6 of the B14 crystal structure.

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2010-09-01
2019-11-16
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