Guanylate-binding protein 1 inhibits nuclear delivery of pseudorabies virus by disrupting structure of actin filaments

Abstract The alphaherpesvirus pseudorabies virus (PRV) is the causative agent of pseudorabies, responsible for severe economic losses to the swine industry worldwide. The interferon-inducible GTPase guanylate-binding protein 1 (GBP1) exhibits antiviral immunity. Our findings show that there is a rob...

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Main Authors: Xiaohua Zhang, Qian Du, Guiyuan Chen, Yiyuan Jiang, Kai Huang, Linghao Li, Dewen Tong, Yong Huang
Format: Article
Language:English
Published: BMC 2023-03-01
Series:Veterinary Research
Subjects:
Online Access:https://doi.org/10.1186/s13567-023-01154-0
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author Xiaohua Zhang
Qian Du
Guiyuan Chen
Yiyuan Jiang
Kai Huang
Linghao Li
Dewen Tong
Yong Huang
author_facet Xiaohua Zhang
Qian Du
Guiyuan Chen
Yiyuan Jiang
Kai Huang
Linghao Li
Dewen Tong
Yong Huang
author_sort Xiaohua Zhang
collection DOAJ
description Abstract The alphaherpesvirus pseudorabies virus (PRV) is the causative agent of pseudorabies, responsible for severe economic losses to the swine industry worldwide. The interferon-inducible GTPase guanylate-binding protein 1 (GBP1) exhibits antiviral immunity. Our findings show that there is a robust upregulation in the expression of porcine GBP1 during PRV infection. GBP1 knockout promotes PRV infection, while GBP1 overexpression restricts it. Importantly, we found that GBP1 impeded the normal structure of actin filaments in a GTPase-dependent manner, preventing PRV virions from reaching the nucleus. We also discovered that viral US3 protein bound GBP1 to interfere with its GTPase activity. Finally, the interaction between US3 and GBP1 requires US3 serine/threonine kinase activity sites and the GTPase domain (aa 1 to 308) of GBP1. Taken together, this study offers fresh perspectives on how PRV manipulates the host’s antiviral immune system.
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spelling doaj.art-f4411f4ef8db48029001851a253aff1c2023-03-22T12:04:12ZengBMCVeterinary Research1297-97162023-03-0154111210.1186/s13567-023-01154-0Guanylate-binding protein 1 inhibits nuclear delivery of pseudorabies virus by disrupting structure of actin filamentsXiaohua Zhang0Qian Du1Guiyuan Chen2Yiyuan Jiang3Kai Huang4Linghao Li5Dewen Tong6Yong Huang7College of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityAbstract The alphaherpesvirus pseudorabies virus (PRV) is the causative agent of pseudorabies, responsible for severe economic losses to the swine industry worldwide. The interferon-inducible GTPase guanylate-binding protein 1 (GBP1) exhibits antiviral immunity. Our findings show that there is a robust upregulation in the expression of porcine GBP1 during PRV infection. GBP1 knockout promotes PRV infection, while GBP1 overexpression restricts it. Importantly, we found that GBP1 impeded the normal structure of actin filaments in a GTPase-dependent manner, preventing PRV virions from reaching the nucleus. We also discovered that viral US3 protein bound GBP1 to interfere with its GTPase activity. Finally, the interaction between US3 and GBP1 requires US3 serine/threonine kinase activity sites and the GTPase domain (aa 1 to 308) of GBP1. Taken together, this study offers fresh perspectives on how PRV manipulates the host’s antiviral immune system.https://doi.org/10.1186/s13567-023-01154-0Pseudorabies virus (PRV)GBP1GTPase activityserine/threonine protein kinase US3actin filaments
spellingShingle Xiaohua Zhang
Qian Du
Guiyuan Chen
Yiyuan Jiang
Kai Huang
Linghao Li
Dewen Tong
Yong Huang
Guanylate-binding protein 1 inhibits nuclear delivery of pseudorabies virus by disrupting structure of actin filaments
Veterinary Research
Pseudorabies virus (PRV)
GBP1
GTPase activity
serine/threonine protein kinase US3
actin filaments
title Guanylate-binding protein 1 inhibits nuclear delivery of pseudorabies virus by disrupting structure of actin filaments
title_full Guanylate-binding protein 1 inhibits nuclear delivery of pseudorabies virus by disrupting structure of actin filaments
title_fullStr Guanylate-binding protein 1 inhibits nuclear delivery of pseudorabies virus by disrupting structure of actin filaments
title_full_unstemmed Guanylate-binding protein 1 inhibits nuclear delivery of pseudorabies virus by disrupting structure of actin filaments
title_short Guanylate-binding protein 1 inhibits nuclear delivery of pseudorabies virus by disrupting structure of actin filaments
title_sort guanylate binding protein 1 inhibits nuclear delivery of pseudorabies virus by disrupting structure of actin filaments
topic Pseudorabies virus (PRV)
GBP1
GTPase activity
serine/threonine protein kinase US3
actin filaments
url https://doi.org/10.1186/s13567-023-01154-0
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