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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Virology

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1587634

Natural mutations in key NLS amino acids regulate nucleoplasmic shuttling and replication efficiency in PRRSV

Provisionally accepted
Xianchang ZhuXianchang Zhu1Yang XiaYang Xia2Qian LeiQian Lei1Yu GanYu Gan1Shenghai JiangShenghai Jiang3Lian HuangLian Huang1Qihu WenQihu Wen1Wei FuWei Fu1Bo ZhangBo Zhang4Yi ZhangYi Zhang4Shanshan XieShanshan Xie5Jida LiJida Li1*
  • 1College of Public Health, Zunyi Medical University, Zunyi, China
  • 2Southwest Guizhou Vocational and Technical College, Xingyi, China
  • 3Department of Preventive Health Care, Yunan District People's Hospital, Yunfu, China
  • 4College of Basic Medicine, Zunyi Medical University, Zunyi, China
  • 5College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, China

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Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is a mutant strain of the classic porcine reproductive and respiratory syndrome virus (PRRSV) characterized by high morbidity and mortality rates. Epidemiological analysis revealed a natural mutation and stable inheritance of amino acid 46 (41-PGKKNKK-47 mutated to 41-PGKKNRK-47) in the nuclear localization signal or sequence (NLS) region of the N protein of HP-PRRSV. In this study, we showed that the nucleoplasmic shuttling of the HP-PRRSV N protein was associated with a higher efficiency of viral replication than that of the classical PRRSV. The nuclear transporter receptors KPNB1, KPNA1, KPNA2, KPNA6, and KPNA7 were involved in the nuclear import of the N protein. Additionally, the mRNA expression levels of KPNB1 and KPNA1 differed between the two strains after infecting the Marc-145 cells with these strains. The viral replication efficiency also decreased when expression levels of KPNA1 and/or KPNB1 were lowered. Finally, protein binding simulation and kinetic assay showed that the mutation of key amino acid 46 in the NLS region altered the binding mode and kinetics of the N proteins to KPNA1 and KPNB1. This study elucidates, for the first time, the reasons for the enhanced nucleoplasmic shuttling and replication efficiency of HP-PRRSV from the perspective of protein entry into the nucleus. It also provides a foundational reference for the prevention and control of PRRSV.N protein-F

Keywords: PRRSV, Nucleocapsid protein, NLS, NTR, Nuclear-mass shuttle

Received: 04 Mar 2025; Accepted: 13 Jun 2025.

Copyright: © 2025 Zhu, Xia, Lei, Gan, Jiang, Huang, Wen, Fu, Zhang, Zhang, Xie and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Jida Li, College of Public Health, Zunyi Medical University, Zunyi, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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