title: Avian leukosis virus subgroup J induces VEGF expression via NF-κB/PI3K-dependent IL-6 production.
abstract: Avian leukosis virus subgroup J (ALV-J) is an oncogenic virus causing hemangiomas and myeloid tumors in chickens. Interleukin-6 (IL-6) is a multifunctional pro-inflammatory interleukin involved in many types of cancer. We previously demonstrated that IL-6 expression was induced following ALV-J infection in chickens. The aim of this study is to characterize the mechanism by which ALV-J induces IL-6 expression, and the role of IL-6 in tumor development. Our results demonstrate that ALV-J infection increases IL-6 expression in chicken splenocytes, peripheral blood lymphocytes, and vascular endothelial cells. IL-6 production is induced by the ALV-J envelope protein gp85 and capsid protein p27 via PI3K- and NF-κB-mediated signaling. IL-6 in turn induced expression of vascular endothelial growth factor (VEGF)-A and its receptor, VEGFR-2, in vascular endothelial cells and embryonic vascular tissues. Suppression of IL-6 using siRNA inhibited the ALV-J induced VEGF-A and VEGFR-2 expression in vascular endothelial cells, indicating that the ALV-J-induced VEGF-A/VEGFR-2 expression is mediated by IL-6. As VEGF-A and VEGFR-2 are important factors in oncogenesis, our findings suggest that ALV-J hijacks IL-6 to promote tumorigenesis, and indicate that IL-6 could potentially serve as a therapeutic target in ALV-J infections.
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Avian Viral Diseases programme & UK-China Centre of Excellence on Avian Disease Research, The Pirbright Institute, Ash Road, Pirbright, Surrey, GU24 0NF, UK.
authors.forename: Yongxiu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Guan
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Yongzhen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Qi
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Gao
authors.affiliation: Avian Viral Diseases programme & UK-China Centre of Excellence on Avian Disease Research, The Pirbright Institute, Ash Road, Pirbright, Surrey, GU24 0NF, UK.
authors.forename: Venugopal
authors.initials: V
authors.lastname: Nair
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000818:Animals; D001353:Avian Leukosis / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D001354:Avian Leukosis Virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002645:Chickens; D042783:Endothelial Cells / Q000201:enzymology* / Q000821:virology; D054884:Host-Pathogen Interactions; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000201:enzymology* / Q000821:virology; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D036022:Capsid Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D014759:Viral Envelope Proteins; D058539:Phosphatidylinositol 3-Kinase; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: ALV-J; Immune response; Immunity; Immunology and Microbiology Section; VEGF-A; VEGFR-2; interleukin 6; tumorigenesis