INHIBITION OF NUCLEAR FACTOR KAPPA-B ACTIVATION BY A VIRUS-ENCODED I-KAPPA-B-LIKE PROTEIN

Certain viruses have evolved mechanisms to counteract innate immunity, a host response in which nuclear factor kappa B (NF-kappa B) transcri ption factors play a central role. African swine fever virus encodes a protein of 28.2 kDa containing ankyrin repeats similar to those of ce llular I kappa B proteins, which are inhibitors of NF-kappa B. Transfe ction of the African swine fever virus I kappa B gene inhibited tumor necrosis factor-or phorbol ester-induced activation of kappa B- but no t AP-l-driven reporter genes. Moreover, African swine fever virus I ka ppa B co-immunoprecipitated with p65 NF-kappa B, and the purified reco mbinant protein prevented the binding of p65-p50 NF-kappa B proteins t o their target sequences in the DNA. NF-kappa B activation induced by tumor necrosis factor, as detected by mobility shift assays or by tran sfection of kappa B-driven reporter genes, is impaired in African swin e 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 re sponse during viral infection.