Construction of a Dengue NanoLuc Reporter Virus for In Vivo Live Imaging in Mice
Since the first isolation in 1943, the dengue virus (DENV) has spread throughout the world, but effective antiviral drugs or vaccines are still not available. To provide a more stable reporter DENV for vaccine development and antiviral drug screening, we constructed a reporter DENV containing the Na...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/14/6/1253 |
| _version_ | 1797481402995834880 |
|---|---|
| author | Enyue Fang Xiaohui Liu Miao Li Jingjing Liu Zelun Zhang Xinyu Liu Xingxing Li Wenjuan Li Qinhua Peng Yongxin Yu Yuhua Li |
| author_facet | Enyue Fang Xiaohui Liu Miao Li Jingjing Liu Zelun Zhang Xinyu Liu Xingxing Li Wenjuan Li Qinhua Peng Yongxin Yu Yuhua Li |
| author_sort | Enyue Fang |
| collection | DOAJ |
| description | Since the first isolation in 1943, the dengue virus (DENV) has spread throughout the world, but effective antiviral drugs or vaccines are still not available. To provide a more stable reporter DENV for vaccine development and antiviral drug screening, we constructed a reporter DENV containing the NanoLuc reporter gene, which was inserted into the 5′ untranslated region and capsid junction region, enabling rapid virus rescue by in vitro ligation. In addition, we established a live imaging mouse model and found that the reporter virus maintained the neurovirulence of prototype DENV before engineering. DENV-4 exhibited dramatically increased neurovirulence following a glycosylation site-defective mutation in the envelope protein. Significant mice mortality with neurological onset symptoms was observed after intracranial infection of wild-type (WT) mice, thus providing a visualization tool for DENV virulence assessment. Using this model, DENV was detected in the intestinal tissues of WT mice after infection, suggesting that intestinal lymphoid tissues play an essential role in DENV pathogenesis. |
| first_indexed | 2024-03-09T22:14:03Z |
| format | Article |
| id | doaj.art-288df64cce33412fa5f3d87c0c5d6e53 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T22:14:03Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-288df64cce33412fa5f3d87c0c5d6e532023-11-23T19:26:17ZengMDPI AGViruses1999-49152022-06-01146125310.3390/v14061253Construction of a Dengue NanoLuc Reporter Virus for In Vivo Live Imaging in MiceEnyue Fang0Xiaohui Liu1Miao Li2Jingjing Liu3Zelun Zhang4Xinyu Liu5Xingxing Li6Wenjuan Li7Qinhua Peng8Yongxin Yu9Yuhua Li10Department of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 102629, ChinaDepartment of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 102629, ChinaDepartment of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 102629, ChinaDepartment of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 102629, ChinaDepartment of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 102629, ChinaDepartment of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 102629, ChinaDepartment of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 102629, ChinaDepartment of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 102629, ChinaDepartment of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 102629, ChinaDepartment of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 102629, ChinaDepartment of Arbovirus Vaccine, National Institutes for Food and Drug Control, Beijing 102629, ChinaSince the first isolation in 1943, the dengue virus (DENV) has spread throughout the world, but effective antiviral drugs or vaccines are still not available. To provide a more stable reporter DENV for vaccine development and antiviral drug screening, we constructed a reporter DENV containing the NanoLuc reporter gene, which was inserted into the 5′ untranslated region and capsid junction region, enabling rapid virus rescue by in vitro ligation. In addition, we established a live imaging mouse model and found that the reporter virus maintained the neurovirulence of prototype DENV before engineering. DENV-4 exhibited dramatically increased neurovirulence following a glycosylation site-defective mutation in the envelope protein. Significant mice mortality with neurological onset symptoms was observed after intracranial infection of wild-type (WT) mice, thus providing a visualization tool for DENV virulence assessment. Using this model, DENV was detected in the intestinal tissues of WT mice after infection, suggesting that intestinal lymphoid tissues play an essential role in DENV pathogenesis.https://www.mdpi.com/1999-4915/14/6/1253flavivirusreporter virusin vivo imagingneurovirulence |
| spellingShingle | Enyue Fang Xiaohui Liu Miao Li Jingjing Liu Zelun Zhang Xinyu Liu Xingxing Li Wenjuan Li Qinhua Peng Yongxin Yu Yuhua Li Construction of a Dengue NanoLuc Reporter Virus for In Vivo Live Imaging in Mice Viruses flavivirus reporter virus in vivo imaging neurovirulence |
| title | Construction of a Dengue NanoLuc Reporter Virus for In Vivo Live Imaging in Mice |
| title_full | Construction of a Dengue NanoLuc Reporter Virus for In Vivo Live Imaging in Mice |
| title_fullStr | Construction of a Dengue NanoLuc Reporter Virus for In Vivo Live Imaging in Mice |
| title_full_unstemmed | Construction of a Dengue NanoLuc Reporter Virus for In Vivo Live Imaging in Mice |
| title_short | Construction of a Dengue NanoLuc Reporter Virus for In Vivo Live Imaging in Mice |
| title_sort | construction of a dengue nanoluc reporter virus for in vivo live imaging in mice |
| topic | flavivirus reporter virus in vivo imaging neurovirulence |
| url | https://www.mdpi.com/1999-4915/14/6/1253 |
| work_keys_str_mv | AT enyuefang constructionofadenguenanolucreportervirusforinvivoliveimaginginmice AT xiaohuiliu constructionofadenguenanolucreportervirusforinvivoliveimaginginmice AT miaoli constructionofadenguenanolucreportervirusforinvivoliveimaginginmice AT jingjingliu constructionofadenguenanolucreportervirusforinvivoliveimaginginmice AT zelunzhang constructionofadenguenanolucreportervirusforinvivoliveimaginginmice AT xinyuliu constructionofadenguenanolucreportervirusforinvivoliveimaginginmice AT xingxingli constructionofadenguenanolucreportervirusforinvivoliveimaginginmice AT wenjuanli constructionofadenguenanolucreportervirusforinvivoliveimaginginmice AT qinhuapeng constructionofadenguenanolucreportervirusforinvivoliveimaginginmice AT yongxinyu constructionofadenguenanolucreportervirusforinvivoliveimaginginmice AT yuhuali constructionofadenguenanolucreportervirusforinvivoliveimaginginmice |