数字农科院2.0

Residues 27T and 297A in VP2 contribute to the enhanced replication and pathogenicity of raccoon dog parvovirus

文献类型： 外文期刊

作者： Xu, Liwen;Cao, Wenyu;Liu, Yawen;Hu, Bo;Zhang, Chengqi;Li, Shuangshuang;Liu, Jiajia;Fu, Jianhai;Zhang, Zichuang;Sun, Yajie;Zhao, Guanyu;Deng, Xiaoyu;Lu, Rongguang;Bai, Xue

作者机构：

关键词： parvovirus;capsid;mutation;pathogenicity;replication;receptor

期刊名称： JOURNAL OF VIROLOGY

ISSN： 0022-538X

年卷期： 2025 年

页码：

收录情况： SCIE（2025版）

摘要： Raccoon dog parvovirus (RDPV) is a highly contagious pathogen causing severe hemorrhagic enteritis that is fatal in young raccoon dogs. Since 2016, epidemiological investigations have documented recurrent outbreaks of RDPV, exhibiting heightened virulence; however, the molecular mechanisms driving this increased pathogenicity remain poorly understood. In this study, an alignment of 67 complete RDPV sequences identified two high-frequency amino acid mutations at positions 27 and 297 in the VP2 capsid protein that distinguish RDPV strains from before and after the 2016 outbreak. We generated a series of variant viruses with single or double amino acid substitutions using infectious cDNA clones from RDPV/CL/2016 (rRDPV-16) and RDPV/FLD/2010 (rRDPV-10) strains. In F81 cells, the mutant virus derived from rRDPV-16 exhibited reduced replication capacity and attachment than the parental strain, whereas mutants derived from rRDPV-10 showed enhanced replication and attachment. Cell-binding assay, ELISA, and biolayer interferometry (BLI) assays demonstrated a significant decrease in binding capacity to the transferrin receptor (TfR) for the rRDPV-16-derived mutant viruses. In raccoon dogs, these mutant viruses displayed reduced pathogenicity, as evidenced by clinical symptoms, viral loads in rectal swabs, and histopathological changes, compared with the parental strain. Molecular docking and dynamics simulations further suggest that the mutation at position 297 may alter the structural stability of VP2 and affect its binding affinity to raccoon dog TfR (RDTfR). This study identifies amino acid residues at positions 27 and 297 in VP2 as crucial determinants of RDPV replication and pathogenicity, providing insights for the development of therapeutic and prognostic strategies.IMPORTANCERaccoon dog parvovirus (RDPV), a variant of canine parvovirus 2 (CPV-2), has become an emerging threat to fur-bearing canid populations, causing severe disease outbreaks and economic losses. Despite its significance, the molecular basis underlying the enhanced pathogenicity of recent RDPV strains remains poorly understood. Our study identifies two key amino acid mutations (S27T and S297A) in the capsid protein VP2 that significantly increase viral replication, receptor binding affinity, and disease severity in raccoon dogs. These findings elucidate critical determinants of host adaptation and virulence in RDPV, highlighting the evolutionary dynamics of parvoviruses and offering a foundation for targeted antiviral strategies and disease control in fur animal farming.

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