Orf Virus 002 Protein Targets Ovine Protein S100A4 and Inhibits NF-κB 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-κB-p65 at Ser(276) 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.
Institute of Antibody Engineering, School of Biotechnology, Southern Medical UniversityGuangzhou, China; State Key Laboratory of Organ Failure, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Biotechnology, Southern Medical UniversityGuangzhou, China.
Daxiang
D
Chen
Institute of Antibody Engineering, School of Biotechnology, Southern Medical UniversityGuangzhou, China; State Key Laboratory of Organ Failure, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Biotechnology, Southern Medical UniversityGuangzhou, China.
Zewei
Z
Zheng
Institute of Antibody Engineering, School of Biotechnology, Southern Medical UniversityGuangzhou, China; State Key Laboratory of Organ Failure, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Biotechnology, Southern Medical UniversityGuangzhou, China.
Bin
B
Xiao
Institute of Antibody Engineering, School of Biotechnology, Southern Medical UniversityGuangzhou, China; State Key Laboratory of Organ Failure, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Biotechnology, Southern Medical UniversityGuangzhou, China.
Wei
W
Li
Institute of Antibody Engineering, School of Biotechnology, Southern Medical UniversityGuangzhou, China; State Key Laboratory of Organ Failure, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Biotechnology, Southern Medical UniversityGuangzhou, China.
Mingjian
M
Long
Institute of Antibody Engineering, School of Biotechnology, Southern Medical UniversityGuangzhou, China; State Key Laboratory of Organ Failure, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Biotechnology, Southern Medical UniversityGuangzhou, China.
Huiqin
H
Chen
Institute of Antibody Engineering, School of Biotechnology, Southern Medical UniversityGuangzhou, China; State Key Laboratory of Organ Failure, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Biotechnology, Southern Medical UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical UniversityGuangzhou, China.
Ming
M
Li
Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana IL, USA.
Daniel L
DL
Rock
Institute of Antibody Engineering, School of Biotechnology, Southern Medical UniversityGuangzhou, China; State Key Laboratory of Organ Failure, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Biotechnology, Southern Medical UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical UniversityGuangzhou, China.
Wenbo
W
Hao
Institute of Antibody Engineering, School of Biotechnology, Southern Medical UniversityGuangzhou, China; State Key Laboratory of Organ Failure, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Biotechnology, Southern Medical UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical UniversityGuangzhou, China.
Shuhong
S
Luo
NF-κB; ORFV002; S100A4; inhibition; interaction; yeast two-hybrid
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