Inhibition of Nuclear Factor κB Activation by a Virus-encoded IκB-like Protein

Abstract

Certain viruses have evolved mechanisms to counteract innate immunity, a host response in which nuclear factor kappaB (NF-kappaB) 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 IkappaB proteins, which are inhibitors of NF-kappaB. Transfection of the African swine fever virus IkappaB gene inhibited tumor necrosis factor- or phorbol ester-induced activation of kappaB- but not AP-1-driven reporter genes. Moreover, African swine fever virus IkappaB co-immunoprecipitated with p65 NF-kappaB, and the purified recombinant protein prevented the binding of p65-p50 NF-kappaB proteins to their target sequences in the DNA. NF-kappaB activation induced by tumor necrosis factor, as detected by mobility shift assays or by transfection of kappaB-driven reporter genes, is impaired in African swine fever virus-infected cells. These results indicate that the African swine fever virus IkappaB gene homologue interferes with NF-kappaB activation, likely representing a new mechanism to evade the immune response during viral infection.