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

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. Spec...

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Detalles Bibliográficos
Autores principales: Wang, Sheng, Li, Haoyang, Weng, Shaoping, Li, Chaozheng, He, Jianguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941876/
https://www.ncbi.nlm.nih.gov/pubmed/31884168
http://dx.doi.org/10.1016/j.isci.2019.100752
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author Wang, Sheng
Li, Haoyang
Weng, Shaoping
Li, Chaozheng
He, Jianguo
author_facet Wang, Sheng
Li, Haoyang
Weng, Shaoping
Li, Chaozheng
He, Jianguo
author_sort Wang, Sheng
collection PubMed
description 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.
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spelling pubmed-69418762020-01-06 White Spot Syndrome Virus Establishes a Novel IE1/JNK/c-Jun Positive Feedback Loop to Drive Replication Wang, Sheng Li, Haoyang Weng, Shaoping Li, Chaozheng He, Jianguo iScience Article 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. Elsevier 2019-11-30 /pmc/articles/PMC6941876/ /pubmed/31884168 http://dx.doi.org/10.1016/j.isci.2019.100752 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Sheng
Li, Haoyang
Weng, Shaoping
Li, Chaozheng
He, Jianguo
White Spot Syndrome Virus Establishes a Novel IE1/JNK/c-Jun Positive Feedback Loop to Drive Replication
title White Spot Syndrome Virus Establishes a Novel IE1/JNK/c-Jun Positive Feedback Loop to Drive Replication
title_full White Spot Syndrome Virus Establishes a Novel IE1/JNK/c-Jun Positive Feedback Loop to Drive Replication
title_fullStr White Spot Syndrome Virus Establishes a Novel IE1/JNK/c-Jun Positive Feedback Loop to Drive Replication
title_full_unstemmed White Spot Syndrome Virus Establishes a Novel IE1/JNK/c-Jun Positive Feedback Loop to Drive Replication
title_short White Spot Syndrome Virus Establishes a Novel IE1/JNK/c-Jun Positive Feedback Loop to Drive Replication
title_sort white spot syndrome virus establishes a novel ie1/jnk/c-jun positive feedback loop to drive replication
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941876/
https://www.ncbi.nlm.nih.gov/pubmed/31884168
http://dx.doi.org/10.1016/j.isci.2019.100752
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