Inhibition of nuclear factor κB activation by a virus-encoded IκB-like protein

Certain viruses have evolved mechanisms to counteract innate immunity, a host response in which nuclear factor kappa B (NF-kappa B) transcription factors play a central role. African swine fever virus encodes a protein of 28.2 kDa containing ankyrin repeats similar to those of cellular I kappa B proteins, which are inhibitors of NF-kappa B. Transfection of the African swine fever virus I kappa B gene inhibited tumor necrosis factor-or phorbol ester-induced activation of kappa B- but not AP-l-driven reporter genes. Moreover, African swine fever virus I kappa B co-immunoprecipitated with p65 NF-kappa B, and the purified recombinant protein prevented the binding of p65-p50 NF-kappa B proteins to their target sequences in the DNA. NF-kappa B activation induced by tumor necrosis factor, as detected by mobility shift assays or by transfection of kappa B-driven reporter genes, is impaired in African swine fever virus-infected cells. These results indicate that the African swine fever virus I kappa B gene homologue interferes with NF-kappa B activation, likely representing a new mechanism to evade the immune response during viral infection.