Borna disease virus possesses an NF-κ B inhibitory sequence in the nucleoprotein gene

Akiko Makino, Kan Fujino, Nicholas F. Parrish, Tomoyuki Honda, Keizo Tomonaga

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number8696
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • General

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