Orf virus 002 protein targets ovine protein S100A4 and inhibits NF-kappa B signaling
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-kB-p65 at Ser276 and also to disru...
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doaj-64a51ce4febf42f98c7097f7009daac62020-11-24T23:45:21ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-09-01710.3389/fmicb.2016.01389198143Orf virus 002 protein targets ovine protein S100A4 and inhibits NF-kappa B signalingDaxiang Chen0Zewei Zheng1Bin Xiao2Wei Li3Mingjian Long4Huiqin Chen5Ming Li6Daniel L Rock7Wenbo Hao8Shuhong Luo9Southern Medical UniversitySouthern Medical UniversitySouthern Medical UniversitySouthern Medical UniversitySouthern Medical UniversitySouthern Medical UniversitySouthern Medical UniversityUniversity of Illinois at Champaign-UrbanaSouthern Medical UniversitySouthern Medical UniversityOrf 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-kB-p65 at Ser276 and also to disrupt the binding of NF-kB-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), prolylendopeptidase-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 ovine S100A4 participating 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.http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01389/fullinhibitionInteractionNF-κByeast two-hybridS100A4ORFV002 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daxiang Chen Zewei Zheng Bin Xiao Wei Li Mingjian Long Huiqin Chen Ming Li Daniel L Rock Wenbo Hao Shuhong Luo |
spellingShingle |
Daxiang Chen Zewei Zheng Bin Xiao Wei Li Mingjian Long Huiqin Chen Ming Li Daniel L Rock Wenbo Hao Shuhong Luo Orf virus 002 protein targets ovine protein S100A4 and inhibits NF-kappa B signaling Frontiers in Microbiology inhibition Interaction NF-κB yeast two-hybrid S100A4 ORFV002 |
author_facet |
Daxiang Chen Zewei Zheng Bin Xiao Wei Li Mingjian Long Huiqin Chen Ming Li Daniel L Rock Wenbo Hao Shuhong Luo |
author_sort |
Daxiang Chen |
title |
Orf virus 002 protein targets ovine protein S100A4 and inhibits NF-kappa B signaling |
title_short |
Orf virus 002 protein targets ovine protein S100A4 and inhibits NF-kappa B signaling |
title_full |
Orf virus 002 protein targets ovine protein S100A4 and inhibits NF-kappa B signaling |
title_fullStr |
Orf virus 002 protein targets ovine protein S100A4 and inhibits NF-kappa B signaling |
title_full_unstemmed |
Orf virus 002 protein targets ovine protein S100A4 and inhibits NF-kappa B signaling |
title_sort |
orf virus 002 protein targets ovine protein s100a4 and inhibits nf-kappa b signaling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Microbiology |
issn |
1664-302X |
publishDate |
2016-09-01 |
description |
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-kB-p65 at Ser276 and also to disrupt the binding of NF-kB-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), prolylendopeptidase-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 ovine S100A4 participating 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. |
topic |
inhibition Interaction NF-κB yeast two-hybrid S100A4 ORFV002 |
url |
http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01389/full |
work_keys_str_mv |
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