Cooperative nuclear import of duck plague virus DNA polymerase subunits: pUL42 NLS Enhances pUL30 nuclear import and viral replication, with VP22 as a compensatory factor
Duck plague (DP), caused by duck plague virus (DPV), is an acute, febrile, and septic disease fatal to geese, ducks, and other wild waterfowl. The DPV UL42 gene product, pUL42, an accessory subunit of the viral DNA polymerase, whose nuclear import is critical for viral replication; however, the underlying mechanism remains unclear. In this study, we identified a 33-amino acids region at the C-terminus of pUL42, containing its nuclear localization signal (NLS). This NLS not only mediated the nuclear entry of pUL42, but also promoted the nuclear import of the DNA polymerase catalytic subunit pUL30. The deletion of this region impaired viral replication. Furthermore, we discovered that the viral protein VP22 alleviates the nuclear import defect of NLS-deficient pUL42 through compensatory nuclear trafficking facilitation. Our findings revealed the first mechanistic model for DPV pUL42 nuclear translocation, offering insights into conserved herpesvirus replication mechanisms and highlighting potential antiviral strategies targeting the pUL42-VP22 transport axis.
Authors
- Shun Chen (ORCID: https://orcid.org/0000-0003-0097-2654)
- Qiao Yang (ORCID: https://orcid.org/0000-0001-7401-2168)
- Renyong Jia
- Mafeng Liu (ORCID: https://orcid.org/0000-0002-6834-3128)
- Yanling Yu (ORCID: https://orcid.org/0000-0003-1477-7382)
- Shaqiu Zhang
- Bin Tian (ORCID: https://orcid.org/0000-0002-2700-7945)
- Di Sun (ORCID: https://orcid.org/0000-0002-7992-1771)
- Xinxin Zhao (ORCID: https://orcid.org/0000-0002-1901-1784)
- Zhen Wu (ORCID: https://orcid.org/0000-0003-2235-825X)
- Ling Zhang (ORCID: https://orcid.org/0000-0002-4881-3989)
- Juan Huang (ORCID: https://orcid.org/0000-0003-3072-4352)
- Yu He (ORCID: https://orcid.org/0000-0001-9616-5261)
- Ying Wu (ORCID: https://orcid.org/0000-0003-3801-4638)
- Mingshu Wang
- Anchun Cheng
- Xumin Ou
- Yuxi Cui
- Dekang Zhu
Institutions
- Sichuan Agricultural University (CN)
- Sichuan Center for Disease Control and Prevention (CN)
Publication Details
- Journal
- Veterinary Microbiology
- Published
- 2025-06-13
- DOI
- https://doi.org/10.1016/j.vetmic.2025.110603
- Primary Topic
- Herpesvirus Infections and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Agriculture Research System of China
- Ministry of Agriculture and Rural Affairs of the People's Republic of China
- Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System