title: Interaction of the Small GTPase Cdc42 with Arginine Kinase Restricts White Spot Syndrome Virus in Shrimp.
abstract: Many types of small GTPases are widely expressed in eukaryotes and have different functions. As a crucial member of the Rho GTPase family, Cdc42 serves a number of functions, such as regulating cell growth, migration, and cell movement. Several RNA viruses employ Cdc42-hijacking tactics in their target cell entry processes. However, the function of Cdc42 in shrimp antiviral immunity is not clear. In this study, we identified a Cdc42 protein in the kuruma shrimp (Marsupenaeus japonicus) and named itMjCdc42.MjCdc42 was upregulated in shrimp challenged by white spot syndrome virus (WSSV). The knockdown ofMjCdc42 and injection of Cdc42 inhibitors increased the proliferation of WSSV. Further experiments determined thatMjCdc42 interacted with an arginine kinase (MjAK). By analyzing the binding activity and enzyme activity ofMjAK and its mutant, ΔMjAK, we found thatMjAK could enhance the replication of WSSV in shrimp.MjAK interacted with the envelope protein VP26 of WSSV. An inhibitor of AK activity, quercetin, could impair the function ofMjAK in WSSV replication. Further study demonstrated that the binding ofMjCdc42 andMjAK depends on Cys271ofMjAK and suppresses the WSSV replication-promoting effect ofMjAK. By interacting with the active site ofMjAK and suppressing its enzyme activity,MjCdc42 inhibits WSSV replication in shrimp. Our results demonstrate a new function of Cdc42 in the cellular defense against viral infection in addition to the regulation of actin and phagocytosis, which has been reported in previous studies.IMPORTANCEThe interaction of Cdc42 with arginine kinase plays a crucial role in the host defense against WSSV infection. This study identifies a new mechanism of Cdc42 in innate immunity and enriches the knowledge of the antiviral innate immunity of invertebrates.
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Shandong, China.
authors.forename: Ji-Dong
authors.initials: JD
authors.lastname: Xu
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Shandong, China.
authors.forename: Hai-Shan
authors.initials: HS
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Shandong, China.
authors.forename: Tian-Di
authors.initials: TD
authors.lastname: Wei
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Shandong, China.
authors.forename: Ke-Yi
authors.initials: KY
authors.lastname: Zhang
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Shandong, China.
authors.forename: Xian-Wei
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Shandong, China.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Zhao
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Shandong, China jxwang@sdu.edu.cn.
authors.forename: Jin-Xing
authors.initials: JX
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001122:Arginine Kinase / Q000737:chemistry / Q000378:metabolism*; D060829:Arthropod Proteins / Q000737:chemistry / Q000378:metabolism*; D017124:Conserved Sequence; D004790:Enzyme Induction / Q000276:immunology; D004926:Escherichia coli; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D062105:Molecular Docking Simulation; D033561:Penaeidae / Q000201:enzymology / Q000276:immunology / Q000821:virology*; D011485:Protein Binding; D060066:Protein Interaction Maps; D015854:Up-Regulation; D014779:Virus Replication; D046848:White spot syndrome virus 1 / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D060829:Arthropod Proteins; D001122:Arginine Kinase; D020764:cdc42 GTP-Binding Protein
keywords: Cdc42; WSSV; arginine kinase; innate immunity; shrimp