Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus

We previously demonstrated that two methyltransferase motifs, K-D-K-E and G-G-D, affect the pathogenicity of Newcastle disease virus (NDV) by regulating mRNA translation and virus transmission. Here, we compared the infectious centre area produced by the NDV strain, rSG10, and methyltransferase moti...

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Main Authors: Xiao Li, Ye Zhao, Qing-Yuan Teng, Xue-Hui Zhang, Jia Xue, Guo-Zhong Zhang
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Virulence
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Online Access:https://www.tandfonline.com/doi/10.1080/21505594.2023.2186336
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author Xiao Li
Ye Zhao
Qing-Yuan Teng
Xue-Hui Zhang
Jia Xue
Guo-Zhong Zhang
author_facet Xiao Li
Ye Zhao
Qing-Yuan Teng
Xue-Hui Zhang
Jia Xue
Guo-Zhong Zhang
author_sort Xiao Li
collection DOAJ
description We previously demonstrated that two methyltransferase motifs, K-D-K-E and G-G-D, affect the pathogenicity of Newcastle disease virus (NDV) by regulating mRNA translation and virus transmission. Here, we compared the infectious centre area produced by the NDV strain, rSG10, and methyltransferase motifs mutant rSG10 strains in DF-1 cells. The results show that intercellular transmission was attenuated by methyltransferase motif mutations. We further determined the ability of mutant viruses to spread in cell-free and cell-to-cell situations. Cell-free transmission of rSG10-K1756A was not reduced, indicating that cell-to-cell transmission of rSG10-K1756A was decreased. Using a donor and target system, we demonstrated that NDV can spread from cell-to-cell directly. Furthermore, by comparing the protein distribution area of three strains when treated with 2% agar overlay, we found that rSG10-K1756A was defective in cell-to-cell transmission. Tunnelling nanotubes (TNTs) are an important mode for cell-to-cell transmission. Treatment of cells with cytochalasin D (CytoD) or nocodazole to inhibit the formation of TNTs, reduced protein levels in all strains, but rSG10-K1756A was the least affected. These results indicate that mutation of the K-D-K-E motif is likely to restricted the spread of NDV via TNTs. Finally, we observed that matrix protein (M) and fusion protein (F) promoted the formation of cellular extensions, which may be involved in the cell-to-cell spread of NDV. Our research reveals a novel mechanism by which methyltransferase motifs affect the cell-to-cell spread of NDV and provides insight into dissemination of paramyxoviruses.
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issn 2150-5594
2150-5608
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publishDate 2023-12-01
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series Virulence
spelling doaj-art-6dbc930ccd29431486d2e6df8dbd57fc2025-08-20T03:24:52ZengTaylor & Francis GroupVirulence2150-55942150-56082023-12-0114110.1080/21505594.2023.2186336Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virusXiao Li0Ye Zhao1Qing-Yuan Teng2Xue-Hui Zhang3Jia Xue4Guo-Zhong Zhang5Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaKey Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaKey Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaKey Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaKey Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaKey Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaWe previously demonstrated that two methyltransferase motifs, K-D-K-E and G-G-D, affect the pathogenicity of Newcastle disease virus (NDV) by regulating mRNA translation and virus transmission. Here, we compared the infectious centre area produced by the NDV strain, rSG10, and methyltransferase motifs mutant rSG10 strains in DF-1 cells. The results show that intercellular transmission was attenuated by methyltransferase motif mutations. We further determined the ability of mutant viruses to spread in cell-free and cell-to-cell situations. Cell-free transmission of rSG10-K1756A was not reduced, indicating that cell-to-cell transmission of rSG10-K1756A was decreased. Using a donor and target system, we demonstrated that NDV can spread from cell-to-cell directly. Furthermore, by comparing the protein distribution area of three strains when treated with 2% agar overlay, we found that rSG10-K1756A was defective in cell-to-cell transmission. Tunnelling nanotubes (TNTs) are an important mode for cell-to-cell transmission. Treatment of cells with cytochalasin D (CytoD) or nocodazole to inhibit the formation of TNTs, reduced protein levels in all strains, but rSG10-K1756A was the least affected. These results indicate that mutation of the K-D-K-E motif is likely to restricted the spread of NDV via TNTs. Finally, we observed that matrix protein (M) and fusion protein (F) promoted the formation of cellular extensions, which may be involved in the cell-to-cell spread of NDV. Our research reveals a novel mechanism by which methyltransferase motifs affect the cell-to-cell spread of NDV and provides insight into dissemination of paramyxoviruses.https://www.tandfonline.com/doi/10.1080/21505594.2023.2186336Newcastle disease virusK-D-K-E motifcell-to-celltunnelling nanotubes
spellingShingle Xiao Li
Ye Zhao
Qing-Yuan Teng
Xue-Hui Zhang
Jia Xue
Guo-Zhong Zhang
Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus
Virulence
Newcastle disease virus
K-D-K-E motif
cell-to-cell
tunnelling nanotubes
title Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus
title_full Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus
title_fullStr Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus
title_full_unstemmed Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus
title_short Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus
title_sort methyltransferase k d k e motif influences the intercellular transmission of newcastle disease virus
topic Newcastle disease virus
K-D-K-E motif
cell-to-cell
tunnelling nanotubes
url https://www.tandfonline.com/doi/10.1080/21505594.2023.2186336
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