A point mutation in duck plague virus gB enhances viral fusogenicity and intercellular dissemination via SNAP25-mediated membrane fusion.
- 1Institute of Veterinary Immunology and Green Veterinary Drugs, Veterinary Department in College of Animal Science, State Key Laboratory of Green Pesticide, Guizhou University, Guiyang, 550025, China.
- 2Institute of Veterinary Immunology and Green Veterinary Drugs, Veterinary Department in College of Animal Science, State Key Laboratory of Green Pesticide, Guizhou University, Guiyang, 550025, China. Electronic address: [email protected].
Abstract
Duck plague virus (DPV) is an alphaherpesvirus that causes significant economic losses to the poultry industry. Glycoprotein B (gB) is the core fusogen mediating membrane fusion during viral entry and cell-to-cell spread, yet the regulatory mechanisms governing gB-induced cell fusion in DPV remain poorly understood. In this study, we identified a single alanine-to-valine substitution at residue 942 of DPV gB (A942V) that unleashes the fusogenic potential of gB, leading to extensive syncytium formation in duck embryo fibroblasts. The A942V mutation significantly enhanced viral attachment, entry, and intercellular spread through fusion-mediated cytoplasmic channels, as revealed by transmission electron microscopy. In vivo, the mutant strain showed moderately increased pathogenicity-with survival rates of 60% versus 70% for the parental strain-without fundamentally altering the overall disease course. Proteomic profiling identified synaptosome-associated protein 25 (SNAP25) as a host factor markedly upregulated in DPV-A942V-infected cells. Mechanistically, the A942V mutation strengthened the binding affinity between gB and SNAP25, as corroborated by co-immunoprecipitation and molecular docking analyses (binding free energy: -82.92 kcal/mol; confidence score: 0.9478). Functional studies revealed that SNAP25 alone is sufficient to induce cell fusion, and that both its N- and C-terminal domains support fusion activity, whereas the middle region is functionally dispensable. SNAP25 overexpression enhanced, whereas knockdown reduced, viral proliferation and cell-to-cell spread without affecting viral attachment or entry. Collectively, these findings establish Ala942 of DPV gB as a critical inhibitory determinant of cell fusion and identify SNAP25 as a critical host dependency exploited by DPV to promote intercellular dissemination. Our study provides new insights into the molecular mechanisms of herpesvirus-induced cell fusion and highlights SNAP25 as a potential antiviral target for controlling DPV infection.
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BibTeX
@article{yang2026point,
title = {{A point mutation in duck plague virus gB enhances viral fusogenicity and intercellular dissemination via SNAP25-mediated membrane fusion.}},
author = {Linjiang Yang and Mao Du and Lingfeng Jiang and Zhentao Cheng and Ming Wen and Guilan Wen and Anchun Cheng},
journal = {Poultry science},
year = {2026},
month = oct,
doi = {10.1016/j.psj.2026.107920},
url = {https://europepmc.org/article/MED/42858563},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A point mutation in duck plague virus gB enhances viral fusogenicity and intercellular dissemination via SNAP25-mediated membrane fusion.
AU - Linjiang Yang
AU - Mao Du
AU - Lingfeng Jiang
AU - Zhentao Cheng
AU - Ming Wen
AU - Guilan Wen
AU - Anchun Cheng
PY - 2026
DA - 2026/10/07
JO - Poultry science
DO - 10.1016/j.psj.2026.107920
UR - https://europepmc.org/article/MED/42858563
AB - Duck plague virus (DPV) is an alphaherpesvirus that causes significant economic losses to the poultry industry. Glycoprotein B (gB) is the core fusogen mediating membrane fusion during viral entry and cell-to-cell spread, yet the regulatory mechanisms governing gB-induced cell fusion in DPV remain poorly understood. In this study, we identified a single alanine-to-valine substitution at residue 942 of DPV gB (A942V) that unleashes the fusogenic potential of gB, leading to extensive syncytium formation in duck embryo fibroblasts. The A942V mutation significantly enhanced viral attachment, entry, and intercellular spread through fusion-mediated cytoplasmic channels, as revealed by transmission electron microscopy. In vivo, the mutant strain showed moderately increased pathogenicity-with survival rates of 60% versus 70% for the parental strain-without fundamentally altering the overall disease course. Proteomic profiling identified synaptosome-associated protein 25 (SNAP25) as a host factor markedly upregulated in DPV-A942V-infected cells. Mechanistically, the A942V mutation strengthened the binding affinity between gB and SNAP25, as corroborated by co-immunoprecipitation and molecular docking analyses (binding free energy: -82.92 kcal/mol; confidence score: 0.9478). Functional studies revealed that SNAP25 alone is sufficient to induce cell fusion, and that both its N- and C-terminal domains support fusion activity, whereas the middle region is functionally dispensable. SNAP25 overexpression enhanced, whereas knockdown reduced, viral proliferation and cell-to-cell spread without affecting viral attachment or entry. Collectively, these findings establish Ala942 of DPV gB as a critical inhibitory determinant of cell fusion and identify SNAP25 as a critical host dependency exploited by DPV to promote intercellular dissemination. Our study provides new insights into the molecular mechanisms of herpesvirus-induced cell fusion and highlights SNAP25 as a potential antiviral target for controlling DPV infection.
SN - 0032-5791
SN - 1525-3171
ER -