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Volume 13
Issue 9
10.3390/microorganisms13091969
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Drebrin Is Involved in the Life Cycle of Pseudorabies Virus by Regulating the Actin Cytoskeleton

by
Kun Xu
1,†,
Xiao-Han Wang
1,†,
Yan-Pei Ku
1,
Jie-Yuan Guo
1,
Shu-Han Fan
1,
Miao-Miao Xue
1,
Jiang Wang
1,2,3,4,
Shuang Guo
1,2,3,
Jia-Jia Pan
1,2,3,4,* and
Bei-Bei Chu
1,2,3,4,*
1
College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China
2
Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs of the People’s Republic of China, Zhengzhou 450046, China
3
Key Laboratory of Veterinary Biotechnology of Henan Province, Zhengzhou 450046, China
4
Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450046, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Microorganisms 2025, 13(9), 1969; https://doi.org/10.3390/microorganisms13091969
Submission received: 22 June 2025 / Revised: 9 August 2025 / Accepted: 19 August 2025 / Published: 22 August 2025
(This article belongs to the Section Virology)
Versions Notes

Abstract

Pseudorabies virus (PRV), a highly pathogenic alphaherpesvirus, poses a potential threat to public health and safety due to its broad host range and risk of cross-species transmission. Viruses have evolved multiple strategies to exploit host factors for entry into and survival in host cells. Drebrin is an actin-binding protein that restricts rotavirus entry by inhibiting dynamin-mediated endocytosis. However, its role and mechanism in DNA virus infection, particularly in herpesviruses, remain unexplored. In this study, we investigated the role of Drebrin in PRV infection using pharmacological inhibition (BTP−2) and CRISPR-Cas9-mediated gene knockout. Both the Drebrin inhibitor BTP−2 and gene knockout significantly suppressed PRV replication. Intriguingly, Drebrin exhibited stage-specific effects on the viral life cycle: its inhibition enhanced viral internalization during early infection but impaired viral replication at later stages, suggesting that Drebrin plays a complex role in the regulation of PRV infection. PRV infection partially disrupted actin stress fibers and caused an increase in cell size. Drebrin knockout also altered the host-cell morphology, reduced the cell surface area, and induced actin cytoskeleton rearrangement, which was further modulated in PRV-infected cells. In summary, our data demonstrate that Drebrin functions as a critical host factor governing the entire PRV life cycle by regulating actin cytoskeleton reorganization.
Keywords: Drebrin; actin cytoskeleton; viral life cycle; pseudorabies virus Drebrin; actin cytoskeleton; viral life cycle; pseudorabies virus

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MDPI and ACS Style

Xu, K.; Wang, X.-H.; Ku, Y.-P.; Guo, J.-Y.; Fan, S.-H.; Xue, M.-M.; Wang, J.; Guo, S.; Pan, J.-J.; Chu, B.-B. Drebrin Is Involved in the Life Cycle of Pseudorabies Virus by Regulating the Actin Cytoskeleton. Microorganisms 2025, 13, 1969. https://doi.org/10.3390/microorganisms13091969

AMA Style

Xu K, Wang X-H, Ku Y-P, Guo J-Y, Fan S-H, Xue M-M, Wang J, Guo S, Pan J-J, Chu B-B. Drebrin Is Involved in the Life Cycle of Pseudorabies Virus by Regulating the Actin Cytoskeleton. Microorganisms. 2025; 13(9):1969. https://doi.org/10.3390/microorganisms13091969

Chicago/Turabian Style

Xu, Kun, Xiao-Han Wang, Yan-Pei Ku, Jie-Yuan Guo, Shu-Han Fan, Miao-Miao Xue, Jiang Wang, Shuang Guo, Jia-Jia Pan, and Bei-Bei Chu. 2025. "Drebrin Is Involved in the Life Cycle of Pseudorabies Virus by Regulating the Actin Cytoskeleton" Microorganisms 13, no. 9: 1969. https://doi.org/10.3390/microorganisms13091969

APA Style

Xu, K., Wang, X.-H., Ku, Y.-P., Guo, J.-Y., Fan, S.-H., Xue, M.-M., Wang, J., Guo, S., Pan, J.-J., & Chu, B.-B. (2025). Drebrin Is Involved in the Life Cycle of Pseudorabies Virus by Regulating the Actin Cytoskeleton. Microorganisms, 13(9), 1969. https://doi.org/10.3390/microorganisms13091969

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