Dataset Information

White Spot Syndrome Virus Establishes a Novel IE1/JNK/c-Jun Positive Feedback Loop to Drive Replication.

ABSTRACT: Viruses need to hijack and manipulate host proteins to guarantee their replication. Herein, we uncovered that the DNA virus white spot syndrome virus (WSSV) established a novel positive feedback loop by hijacking the host JNK pathway via its immediate-early 1 (IE1) protein to drive replication. Specifically, the WSSV IE1 bound to host JNK, and enhanced JNK autoactivation by autophosphorylation, and in turn, elevated JNK kinase activity to its substrate c-Jun and induced IE1, which resulted in a viral gene-mediated positive feedback loop. Moreover, the activation of this loop is able to induce wsv056, wsv249, and wsv403, in addition to IE1 itself. Disruption of this loop during WSSV infection by knockdown of JNK, c-Jun or IE1 led to an increased survival rate and lower viral burdens in shrimp. Taken together, this loop may provide a potential target for the development of specific antiviral strategies or agents against WSSV infection.

SUBMITTER: Wang S

PROVIDER: S-EPMC6941876 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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White Spot Syndrome Virus Establishes a Novel IE1/JNK/c-Jun Positive Feedback Loop to Drive Replication.

Wang Sheng S Li Haoyang H Weng Shaoping S Li Chaozheng C He Jianguo J

iScience 20191130 1

Viruses need to hijack and manipulate host proteins to guarantee their replication. Herein, we uncovered that the DNA virus white spot syndrome virus (WSSV) established a novel positive feedback loop by hijacking the host JNK pathway via its immediate-early 1 (IE1) protein to drive replication. Specifically, the WSSV IE1 bound to host JNK, and enhanced JNK autoactivation by autophosphorylation, and in turn, elevated JNK kinase activity to its substrate c-Jun and induced IE1, which resulted in a ...[more]

PMID: 31884168

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Project description:Yin Yang 1 (YY1) is a multifunctional zinc finger transcription factor that regulates many key cellular processes. In this study, we report the cloning of YY1 from Litopenaeus vannamei shrimp (LvYY1). This study shows that LvYY1 is ubiquitously expressed in shrimp tissues, and knockdown of LvYY1 expression by double-stranded RNA (dsRNA) injection in white spot syndrome virus (WSSV)-infected shrimp reduced both mRNA levels of the WSSV immediate early gene ie1 as well as overall copy numbers of the WSSV genome. The cumulative mortality rate of infected shrimp also declined with LvYY1 dsRNA injection. Using an insect cell model, we observed that LvYY1 activates ie1 expression, and a mutation introduced into the ie1 promoter subsequently repressed this capability. Moreover, reporter assay results suggested that LvYY1 is involved in basal transcriptional regulation via an interaction with L. vannamei TATA-binding protein (LvTBP). Electrophoretic mobility shift assay (EMSA) results further indicated that LvYY1 binds to a YY1-binding site in the region between positions -119 and -126 in the ie1 promoter. Chromatin immunoprecipitation analysis also confirmed that LvYY1 binds to the ie1 promoter in WSSV-infected shrimp. Taken together, these results indicate that WSSV uses host LvYY1 to enhance ie1 expression via a YY1-binding site and the TATA box in the ie1 promoter, thereby facilitating lytic activation and viral replication.IMPORTANCE WSSV has long been a scourge of the shrimp industry and remains a serious global threat. Thus, there is a pressing need to understand how the interactions between WSSV and its host drive infection, lytic development, pathogenesis, and mortality. Our successful cloning of L. vannamei YY1 (LvYY1) led to the elucidation of a critical virus-host interaction between LvYY1 and the WSSV immediate early gene ie1 We observed that LvYY1 regulates ie1 expression via a consensus YY1-binding site and TATA box. LvYY1 was also found to interact with L. vannamei TATA-binding protein (LvTBP), which may have an effect on basal transcription. Knockdown of LvYY1 expression inhibited ie1 transcription and subsequently reduced viral DNA replication and decreased cumulative mortality rates of WSSV-infected shrimp. These findings are expected to contribute to future studies involving WSSV-host interactions.

Dataset Information

White Spot Syndrome Virus Establishes a Novel IE1/JNK/c-Jun Positive Feedback Loop to Drive Replication.

Publications

White Spot Syndrome Virus Establishes a Novel IE1/JNK/c-Jun Positive Feedback Loop to Drive Replication.

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