Borna disease virus possesses an NF-κ B 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 I? B kinase (IKK)/NF-? B 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-? B pathway. To elucidate the mechanism for the inhibition of NF-? B activation by BDV infection, we evaluated the cross-talk between BDV infection and the NF-? B pathway. Using Multiple EM for Motif Elicitation analysis, we found that the nucleoproteins of BDV (BDV-N) and NF-? B1 share a common ankyrin-like motif. When THP1-CD14 cells were pre-treated with the identified peptide, NF-? B 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-? B1 p105 into p50. Furthermore, immunoprecipitation assays showed that BDV-N interacted with NF-? B1 but not with NF-? B2, which shares no common motif with BDV-N. These results suggest BDV-N inhibits NF-? B1 processing by the 20S proteasome through its ankyrin-like peptide sequence, resulting in the suppression of IKK/NF-? B pathway activation. This inhibitory effect of BDV on the induction of the host innate immunity might provide benefits against persistent BDV infection.