Borna disease virus possesses an NF-ĸB inhibitory sequence in the nucleoprotein gene.
Borna disease virus (BDV) has a non-segmented, negative-stranded RNA genome and causes persistent infection in many animal species. Previous study has shown that the activation of the IκB kinase (IKK)/NF-κB pathway is reduced by BDV infection even in cells expressing constitutively active mutant IKK. This result suggests that BDV directly interferes with the IKK/NF-κB pathway. To elucidate the mechanism for the inhibition of NF-κB activation by BDV infection, we evaluated the cross-talk between BDV infection and the NF-κB pathway. Using Multiple EM for Motif Elicitation analysis, we found that the nucleoproteins of BDV (BDV-N) and NF-κB1 share a common ankyrin-like motif. When THP1-CD14 cells were pre-treated with the identified peptide, NF-κB activation by Toll-like receptor ligands was suppressed. The 20S proteasome assay showed that BDV-N and BDV-N-derived peptide inhibited the processing of NF-κB1 p105 into p50. Furthermore, immunoprecipitation assays showed that BDV-N interacted with NF-κB1 but not with NF-κB2, which shares no common motif with BDV-N. These results suggest BDV-N inhibits NF-κB1 processing by the 20S proteasome through its ankyrin-like peptide sequence, resulting in the suppression of IKK/NF-κB pathway activation. This inhibitory effect of BDV on the induction of the host innate immunity might provide benefits against persistent BDV infection.
1] Department of Viral Oncology, Kyoto University, Kyoto 606-8507, Japan [2] Center for Emerging Virus Research, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Akiko
A
Makino
Department of Viral Oncology, Kyoto University, Kyoto 606-8507, Japan.
Kan
K
Fujino
Department of Viral Oncology, Kyoto University, Kyoto 606-8507, Japan.
Nicholas F
NF
Parrish
1] Department of Viral Oncology, Kyoto University, Kyoto 606-8507, Japan [2] Department of Tumor Viruses, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Tomoyuki
T
Honda
1] Department of Viral Oncology, Kyoto University, Kyoto 606-8507, Japan [2] Department of Tumor Viruses, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan [3] Department of Mammalian Regulatory Network, Graduate School of Biostudies, Kyoto University, Kyoto 606-8507, Japan.
Keizo
K
Tomonaga
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001890:Borna Disease / Q000378:metabolism / Q000821:virology; D001891:Borna disease virus / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D008958:Models, Molecular; D016328:NF-kappa B / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D015398:Signal Transduction; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D010446:Peptide Fragments; D014764:Viral Proteins; D046988:Proteasome Endopeptidase Complex