Affiliation:
1. Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Shandong, China
2. State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Shandong, China
Abstract
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 it
Mj
Cdc42.
Mj
Cdc42 was upregulated in shrimp challenged by white spot syndrome virus (WSSV). The knockdown of
Mj
Cdc42 and injection of Cdc42 inhibitors increased the proliferation of WSSV. Further experiments determined that
Mj
Cdc42 interacted with an arginine kinase (
Mj
AK). By analyzing the binding activity and enzyme activity of
Mj
AK and its mutant, Δ
Mj
AK, we found that
Mj
AK could enhance the replication of WSSV in shrimp.
Mj
AK interacted with the envelope protein VP26 of WSSV. An inhibitor of AK activity, quercetin, could impair the function of
Mj
AK in WSSV replication. Further study demonstrated that the binding of
Mj
Cdc42 and
Mj
AK depends on Cys
271
of
Mj
AK and suppresses the WSSV replication-promoting effect of
Mj
AK. By interacting with the active site of
Mj
AK and suppressing its enzyme activity,
Mj
Cdc42 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.
IMPORTANCE
The 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.
Funder
National Science Foundation of China
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Cited by
12 articles.
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