The Ablation of Envelope Protein Glycosylation Enhances the Neurovirulence of ZIKV and Cell Apoptosis in Newborn Mice
Zika virus (ZIKV) has attracted the wide global attention due to its causal link to microcephaly. In this study, two amino acid (aa) mutation (E143K and R3394K) were identified at the fourth generation (named ZKC2P4) during the serial passage of ZIKV-Asian lineage ZKC2/2016 strain in the newborn mou...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/5317662 |
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| author | Yanqing Guo Linlin Bao Yanfeng Xu Fengdi Li Qi Lv Feiyue Fan Chuan Qin |
| author_facet | Yanqing Guo Linlin Bao Yanfeng Xu Fengdi Li Qi Lv Feiyue Fan Chuan Qin |
| author_sort | Yanqing Guo |
| collection | DOAJ |
| description | Zika virus (ZIKV) has attracted the wide global attention due to its causal link to microcephaly. In this study, two amino acid (aa) mutation (E143K and R3394K) were identified at the fourth generation (named ZKC2P4) during the serial passage of ZIKV-Asian lineage ZKC2/2016 strain in the newborn mouse brain, while another seven aa deletions in envelope (E) protein were detected in ZKC2P6. ZKC2P6 is a novel nonglycosylated E protein Asian ZIKV we first identified and provides the first direct supporting evidence that glycosylation motif could be lost during the passage in neonatal mice. To study the impact of E protein glycosylation ablation, we compared the pathogenicity of ZKC2P6 with that of ZKC2P4. The results showed that the loss of E protein glycosylation accelerated the disease progression, as evidenced by an earlier weight loss and death, a thinner cerebral cortex, and more serious tissue lesions and inflammation/necrosis. Furthermore, ZKC2P6 exhibited a greater ability to replicate and caused severer cell apoptosis than that of ZKC2P4. Therefore, the ablation of E glycosylation generally enhances the neurovirulence of ZIKV and cell apoptosis in newborn mice. |
| format | Article |
| id | doaj-art-656d79180c35400eb1757d7b215e992f |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-656d79180c35400eb1757d7b215e992f2025-08-20T03:34:36ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/53176625317662The Ablation of Envelope Protein Glycosylation Enhances the Neurovirulence of ZIKV and Cell Apoptosis in Newborn MiceYanqing Guo0Linlin Bao1Yanfeng Xu2Fengdi Li3Qi Lv4Feiyue Fan5Chuan Qin6Comparative Medicine Center, Peking Union Medical College (PUMC) and, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, ChinaComparative Medicine Center, Peking Union Medical College (PUMC) and, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, ChinaComparative Medicine Center, Peking Union Medical College (PUMC) and, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, ChinaComparative Medicine Center, Peking Union Medical College (PUMC) and, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, ChinaComparative Medicine Center, Peking Union Medical College (PUMC) and, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, ChinaComparative Medicine Center, Peking Union Medical College (PUMC) and, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, ChinaComparative Medicine Center, Peking Union Medical College (PUMC) and, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, ChinaZika virus (ZIKV) has attracted the wide global attention due to its causal link to microcephaly. In this study, two amino acid (aa) mutation (E143K and R3394K) were identified at the fourth generation (named ZKC2P4) during the serial passage of ZIKV-Asian lineage ZKC2/2016 strain in the newborn mouse brain, while another seven aa deletions in envelope (E) protein were detected in ZKC2P6. ZKC2P6 is a novel nonglycosylated E protein Asian ZIKV we first identified and provides the first direct supporting evidence that glycosylation motif could be lost during the passage in neonatal mice. To study the impact of E protein glycosylation ablation, we compared the pathogenicity of ZKC2P6 with that of ZKC2P4. The results showed that the loss of E protein glycosylation accelerated the disease progression, as evidenced by an earlier weight loss and death, a thinner cerebral cortex, and more serious tissue lesions and inflammation/necrosis. Furthermore, ZKC2P6 exhibited a greater ability to replicate and caused severer cell apoptosis than that of ZKC2P4. Therefore, the ablation of E glycosylation generally enhances the neurovirulence of ZIKV and cell apoptosis in newborn mice.http://dx.doi.org/10.1155/2021/5317662 |
| spellingShingle | Yanqing Guo Linlin Bao Yanfeng Xu Fengdi Li Qi Lv Feiyue Fan Chuan Qin The Ablation of Envelope Protein Glycosylation Enhances the Neurovirulence of ZIKV and Cell Apoptosis in Newborn Mice Journal of Immunology Research |
| title | The Ablation of Envelope Protein Glycosylation Enhances the Neurovirulence of ZIKV and Cell Apoptosis in Newborn Mice |
| title_full | The Ablation of Envelope Protein Glycosylation Enhances the Neurovirulence of ZIKV and Cell Apoptosis in Newborn Mice |
| title_fullStr | The Ablation of Envelope Protein Glycosylation Enhances the Neurovirulence of ZIKV and Cell Apoptosis in Newborn Mice |
| title_full_unstemmed | The Ablation of Envelope Protein Glycosylation Enhances the Neurovirulence of ZIKV and Cell Apoptosis in Newborn Mice |
| title_short | The Ablation of Envelope Protein Glycosylation Enhances the Neurovirulence of ZIKV and Cell Apoptosis in Newborn Mice |
| title_sort | ablation of envelope protein glycosylation enhances the neurovirulence of zikv and cell apoptosis in newborn mice |
| url | http://dx.doi.org/10.1155/2021/5317662 |
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