Scientific Publications by FDA Staff

J Biol Chem 2005 Jun 24;280(25):24153-8

Proteolytic cleavage of the p65-RelA subunit of NF-kappaB during poliovirus infection.

Neznanov N, Chumakov KM, Neznanova L, Almasan A, Banerjee AK, Gudkov AV

Neznanov N, Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Genet, 9500 Euclid Ave, Cleveland, OH 44195 USA Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Genet, Cleveland, OH 44195 USA Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA

Activation of NF-kappaB during viral infection is one of the critical elements in innate immune response. Several virus-specific factors, such as double-stranded RNA, can trigger host defense mechanisms by inducing NF-kappaB-mediated expression of cytokines and interferons. Early stages of poliovirus infection are also associated with degradation of IkappaB alpha and translocation of NF-kappaB into the nucleus. However, at later stages of poliovirus replication the p65-RelA component of the NF-kappaB complex undergoes a specific cleavage that coincides with the onset of intensive poliovirus protein synthesis and the appearance of the activity of poliovirus protease 3C. Indeed, the p65-RelA amino acid sequence contains the recognition site for 3C, and recombinant protein 3C was shown to be capable of proteolytic cleavage of p65-RelA, generating truncated product similar to that observed during poliovirus infection. Cleavage of p65-RelA occurs during replication of ECHO-1 and rhinovirus 14, suggesting that inactivation of NF-kappaB function by proteolytic cleavage of p65-RelA is the common mechanism by which picornaviruses suppress the innate immune response.