title: Infectious spleen and kidney necrosis virus ORF48R functions as a new viral vascular endothelial growth factor.
abstract: Infectious spleen and kidney necrosis virus (ISKNV) causes a pandemic and serious disease in fish. Infection by ISKNV causes epidermal lesions, in which petechial hemorrhages and abdominal edema are prominent features. ISKNV ORF48R contains a domain similar to that of the platelet-derived growth factor and vascular endothelial growth factor (VEGF) families of proteins. ISKNV ORF48R showed higher similarity to the VEGFs encoded by Megalocytivirus and Parapoxvirus than to those encoded in fish and mammals. We used zebrafish as a model and constructed a recombinant plasmid containing the DNA sequence of ISKNV ORF48R to study ISKNV infection. The plasmid was microinjected into zebrafish embryos at the one-cell stage. Overexpression of the ISKNV ORF48R gene results in pericardial edema and dilation at the tail region of zebrafish embryos, suggesting that ISKNV ORF48R induces vascular permeability. ISKNV ORF48R is also able to stimulate a striking expression of flk1 in the zebrafish dorsal aorta and the axial vein. Furthermore, ISKNV ORF48R, while cooperating with zebrafish VEGF(121), can stimulate more striking expression of flk1 than can either ISKNV ORF48R or zebrafish VEGF(121) alone. However, decreased expression of FLK-1 by gene knockdown results in the disappearance of pericardial edema and dilation at the tail region of zebrafish embryos induced by overexpression of ISKNV ORF48R in the early stages of embryonic development.
authors.affiliation: State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen (Zhongshan) University, 135 Xingang Road West, Guangzhou 510275, People's Republic of China.
authors.forename: Zi-Liang
authors.initials: ZL
authors.lastname: Wang
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Xu
authors.forename: Bai-Liang
authors.initials: BL
authors.lastname: He
authors.forename: Shao-Ping
authors.initials: SP
authors.lastname: Weng
authors.forename: Jia
authors.initials: J
authors.lastname: Xiao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Lin
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: Yu
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: He
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D004487:Edema; D004625:Embryo, Nonmammalian; D005393:Fish Diseases / Q000821:virology*; D010957:Plasmids / Q000008:administration & dosage; D017385:Sequence Homology; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins / Q000008:administration & dosage / Q000502:physiology*; D014780:Viruses / Q000737:chemistry*; D015027:Zebrafish
chemical_list: D042461:Vascular Endothelial Growth Factor A; D014764:Viral Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2