Orf virus 002 protein targets ovine protein S100A4 and inhibits NF-κB signaling

Daxiang Chen, Zewei Zheng, Bin Xiao, Wei Li, Mingjian Long, Huiqin Chen, Ming Li, Daniel L. Rock, Wenbo Hao, Shuhong Luo

Research output: Contribution to journalArticlepeer-review


Orf virus (ORFV), a member of Parapoxvirus, has evolved various strategies to modulate the immune responses of host cells. The ORFV-encoded protein ORFV002, a regulator factor, has been found to inhibit the acetylation of NF-κB-p65 by blocking phosphorylation of NF-κB-p65 at Ser276 and also to disrupt the binding of NF-κB-p65 and p300. To explore the mechanism by which ORFV002 regulates NF-κB signaling, the understanding of ORFV002 potential binding partners in host cells is critical. In this study, ovine S100 calcium binding protein A4 (S100A4), prolyl endopeptidase-like (PREPL) and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 8 (NDUFA8) were found to interact with ORFV002 based on the yeast two-hybrid (Y2H) assay using a cDNA library derived from primary ovine fetal turbinate cells (OFTu). GST pull-down and bidirectional co-immunoprecipitation assay results demonstrate that ORFV002 interacts with S100A4 directly. Following the pEGFP-ORFV002 (p002GFP) transfection, we found that cytoplasmic S100A4 translocates into the nucleus and co-localizes with ORFV002. Furthermore, the inhibitory effect of ORFV002 on NF-κB signaling was significantly restored by S100A4 knock-down phenotype, suggesting that ovine S100A4 participates in the ORFV002-mediated NF-κB signaling. These data demonstrate that ORFV002 inhibits the NF-κB activation through its interaction with S100A4 along with its nucleus translocation.

Original languageEnglish (US)
Article number1389
JournalFrontiers in Microbiology
Issue numberSEP
StatePublished - Sep 13 2016


  • Inhibition
  • Interaction
  • NF-κB
  • ORFV002
  • S100A4
  • Yeast two-hybrid

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)


Dive into the research topics of 'Orf virus 002 protein targets ovine protein S100A4 and inhibits NF-κB signaling'. Together they form a unique fingerprint.

Cite this