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