The H protein of attenuated canine distemper virus is degraded via endoplasmic reticulum-associated protein degradation
Canine distemper (CD) caused by canine distemper virus (CDV) is considered a highly contagious and acutely febrile disease in various animals around the world. Endoplasmic reticulum-associated protein degradation (ERAD) is an important biological effect induced by endoplasmic reticulum (ER) stress (...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2023.1214318/full |
| _version_ | 1797785683195068416 |
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| author | Wenjie Wang Wenjie Wang Zhenwei Bi Yakun Liu Xingxia Xia Jing Qian Yeping Tan Jianjun Zhao Suquan Song |
| author_facet | Wenjie Wang Wenjie Wang Zhenwei Bi Yakun Liu Xingxia Xia Jing Qian Yeping Tan Jianjun Zhao Suquan Song |
| author_sort | Wenjie Wang |
| collection | DOAJ |
| description | Canine distemper (CD) caused by canine distemper virus (CDV) is considered a highly contagious and acutely febrile disease in various animals around the world. Endoplasmic reticulum-associated protein degradation (ERAD) is an important biological effect induced by endoplasmic reticulum (ER) stress (ERS) for the degradation of unfolded/misfolded proteins in the ER of cells. CDV H glycoprotein is translocated into the ER for post-translational modifications. The effects of CDV H and ER on each other are unclear. In this study, we found that CDV H protein induced ERS through the PERK-mediated signaling pathway. The inhibition of ERS by 4-Phenylbutyric acid (4-PBA) increased the H protein amounts of an attenuated CDV, which was reduced by dithiothreitol (DTT)-induced ERS. Further, the H protein levels were increased when ERAD was inhibited by using Eeyarestatin I or interfering E3 ligase Hrd1 in ERAD, suggesting that the attenuated CDV H protein is degraded via ERAD. ERAD involved ubiquitin-dependent proteasome degradation (UPD) and/or autophagic-lysosome degradation (ALD). The attenuated CDV H protein was ubiquitinated and significantly increased after treatment with UPD inhibitor MG132 but not ALD inhibitor chloroquine (CQ), suggesting that ERAD degrading the attenuated CDV H protein selectively depends on UPD. Moreover, the inhibition of the degradation of CDV H protein with 4-PBA or MG132 treatment increased viral replication, whereas treatment with DTT promoting degradation of H protein was found to reduce viral replication. These findings suggest that the degradation of CDV H protein via ERAD negatively affects viral replication and provide a new idea for developing CDV prevention and control strategies. |
| first_indexed | 2024-03-13T00:57:28Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-03-13T00:57:28Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj.art-cf9158905b5543a19925ac02106290b12023-07-06T16:45:47ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692023-07-011010.3389/fvets.2023.12143181214318The H protein of attenuated canine distemper virus is degraded via endoplasmic reticulum-associated protein degradationWenjie Wang0Wenjie Wang1Zhenwei Bi2Yakun Liu3Xingxia Xia4Jing Qian5Yeping Tan6Jianjun Zhao7Suquan Song8MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, ChinaInstitute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture and Rural Affairs, National Center for Engineering Research of Veterinary Bio-Products, Nanjing, Jiangsu, ChinaInstitute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture and Rural Affairs, National Center for Engineering Research of Veterinary Bio-Products, Nanjing, Jiangsu, ChinaCollege of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, ChinaInstitute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture and Rural Affairs, National Center for Engineering Research of Veterinary Bio-Products, Nanjing, Jiangsu, ChinaInstitute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture and Rural Affairs, National Center for Engineering Research of Veterinary Bio-Products, Nanjing, Jiangsu, ChinaInstitute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture and Rural Affairs, National Center for Engineering Research of Veterinary Bio-Products, Nanjing, Jiangsu, ChinaCollege of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, ChinaMOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, ChinaCanine distemper (CD) caused by canine distemper virus (CDV) is considered a highly contagious and acutely febrile disease in various animals around the world. Endoplasmic reticulum-associated protein degradation (ERAD) is an important biological effect induced by endoplasmic reticulum (ER) stress (ERS) for the degradation of unfolded/misfolded proteins in the ER of cells. CDV H glycoprotein is translocated into the ER for post-translational modifications. The effects of CDV H and ER on each other are unclear. In this study, we found that CDV H protein induced ERS through the PERK-mediated signaling pathway. The inhibition of ERS by 4-Phenylbutyric acid (4-PBA) increased the H protein amounts of an attenuated CDV, which was reduced by dithiothreitol (DTT)-induced ERS. Further, the H protein levels were increased when ERAD was inhibited by using Eeyarestatin I or interfering E3 ligase Hrd1 in ERAD, suggesting that the attenuated CDV H protein is degraded via ERAD. ERAD involved ubiquitin-dependent proteasome degradation (UPD) and/or autophagic-lysosome degradation (ALD). The attenuated CDV H protein was ubiquitinated and significantly increased after treatment with UPD inhibitor MG132 but not ALD inhibitor chloroquine (CQ), suggesting that ERAD degrading the attenuated CDV H protein selectively depends on UPD. Moreover, the inhibition of the degradation of CDV H protein with 4-PBA or MG132 treatment increased viral replication, whereas treatment with DTT promoting degradation of H protein was found to reduce viral replication. These findings suggest that the degradation of CDV H protein via ERAD negatively affects viral replication and provide a new idea for developing CDV prevention and control strategies.https://www.frontiersin.org/articles/10.3389/fvets.2023.1214318/fullcanine distemper virusH proteindegradationERADreplication |
| spellingShingle | Wenjie Wang Wenjie Wang Zhenwei Bi Yakun Liu Xingxia Xia Jing Qian Yeping Tan Jianjun Zhao Suquan Song The H protein of attenuated canine distemper virus is degraded via endoplasmic reticulum-associated protein degradation Frontiers in Veterinary Science canine distemper virus H protein degradation ERAD replication |
| title | The H protein of attenuated canine distemper virus is degraded via endoplasmic reticulum-associated protein degradation |
| title_full | The H protein of attenuated canine distemper virus is degraded via endoplasmic reticulum-associated protein degradation |
| title_fullStr | The H protein of attenuated canine distemper virus is degraded via endoplasmic reticulum-associated protein degradation |
| title_full_unstemmed | The H protein of attenuated canine distemper virus is degraded via endoplasmic reticulum-associated protein degradation |
| title_short | The H protein of attenuated canine distemper virus is degraded via endoplasmic reticulum-associated protein degradation |
| title_sort | h protein of attenuated canine distemper virus is degraded via endoplasmic reticulum associated protein degradation |
| topic | canine distemper virus H protein degradation ERAD replication |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2023.1214318/full |
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