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...
Main Authors: | , , , , , , , |
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Format: | Article |
Language: | English |
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BMC
2023-03-01
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Series: | Veterinary Research |
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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. |
first_indexed | 2024-04-09T22:43:12Z |
format | Article |
id | doaj.art-f4411f4ef8db48029001851a253aff1c |
institution | Directory Open Access Journal |
issn | 1297-9716 |
language | English |
last_indexed | 2024-04-09T22:43:12Z |
publishDate | 2023-03-01 |
publisher | BMC |
record_format | Article |
series | Veterinary Research |
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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