title: The shrimp IKK-NF-κB signaling pathway regulates antimicrobial peptide expression and may be subverted by white spot syndrome virus to facilitate viral gene expression.
abstract: The IκB kinases IKKα and IKKβ and the IKK-related kinases TANK-binding kinase 1 (TBK1) and IKKε are the master regulators of the NF-κB signaling pathway. Although this pathway has been extensively studied in mammals, less attention has been paid in crustaceans, which have significant economic value. Here, we report the cloning and functional studies of two IKK homologs, LvIKKβ and LvIKKε, from Pacific white shrimp, Litopenaeus vannamei. LvIKKβ and LvIKKε mRNAs are widely expressed in different tissues and are responsive to white spot syndrome virus (WSSV) infection. When overexpressed in Drosophila S2 cells, LvIKKβ but not LvIKKε activates the promoters of NF-κB pathway-controlled antimicrobial peptide genes (AMPs), such as the Penaeidins (PENs). In HEK 293T cells, both LvIKKβ and LvIKKε activate an NF-κB reporter. The silencing of LvIKKβ or LvIKKε using double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) decreases the expression of L. vannamei AMPs, including PENs, lysozyme and crustins. Intriguingly, LvIKKβ- or LvIKKε-silenced L. vannamei are resistant to WSSV infection. We hypothesized that successful infection with WSSV requires the activation of the IKK-NF-κB signaling pathway to modulate viral gene expression. We constructed luciferase reporters for 147 WSSV genes. By screening, we found that the WSV051, WSV059, WSV069, WSV083, WSV090, WSV107, WSV244, WSV303, WSV371 and WSV445 promoters can be activated by LvIKKβ or LvIKKε in Drosophila S2 cells. Taken together, our results reveal that LvIKKβ and LvIKKε may participate in the regulation of shrimp AMPs and that WSSV may subvert the L. vannamei IKK-NF-κB signaling pathway to facilitate viral gene expression.
authors: MOE Key Laboratory of Aquatic Product Safety/State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China.
authors: Pei-Hui
authors: PH
authors: Wang
authors: Zhi-Hua
authors: ZH
authors: Gu
authors: Ding-Hui
authors: DH
authors: Wan
authors: Bo-Du
authors: BD
authors: Liu
authors: Xian-De
authors: XD
authors: Huang
authors: Shao-Ping
authors: SP
authors: Weng
authors: Xiao-Qiang
authors: XQ
authors: Yu
authors: Jian-Guo
authors: JG
authors: He
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D004331:Drosophila melanogaster / Q000166:cytology; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D017930:Genes, Reporter; D054884:Host-Pathogen Interactions; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009113:Muramidase / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D033561:Penaeidae / Q000235:genetics / Q000276:immunology* / Q000821:virology; D011401:Promoter Regions, Genetic; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D046848:White spot syndrome virus 1 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D011994:Recombinant Proteins; D008156:Luciferases; D051550:I-kappa B Kinase; D009113:Muramidase
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