title: Proteolytic cleavage of the p65-RelA subunit of NF-kappaB during poliovirus infection.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. neznann@ccf.org
authors.forename: Nickolay
authors.initials: N
authors.lastname: Neznanov
authors.forename: Konstantin M
authors.initials: KM
authors.lastname: Chumakov
authors.forename: Lubov
authors.initials: L
authors.lastname: Neznanova
authors.forename: Alexandru
authors.initials: A
authors.lastname: Almasan
authors.forename: Amiya K
authors.initials: AK
authors.lastname: Banerjee
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Gudkov
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism*; D011051:Poliomyelitis / Q000378:metabolism*; D051996:Transcription Factor RelA
chemical_list: D017931:DNA Primers; D016328:NF-kappa B; D051996:Transcription Factor RelA