Genetic Diversity Does Not Contribute to Attenuation of HeLa Passaged Wild-Type Yellow Fever Virus Strain French Viscerotropic Virus
The disease yellow fever was prevented by two live attenuated vaccines, strains 17D and French neurotropic vaccine (FNV), derived by serial passage of wild-type (WT) strains Asibi and French Viscerotropic virus (FVV), respectively. Both 17D and FNV displayed decreased genetic diversity and resistanc...
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MDPI AG
2022-03-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/3/527 |
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| author | Ashley E. Strother Jill K. Thompson Steven G. Widen Alan D. T. Barrett |
| author_facet | Ashley E. Strother Jill K. Thompson Steven G. Widen Alan D. T. Barrett |
| author_sort | Ashley E. Strother |
| collection | DOAJ |
| description | The disease yellow fever was prevented by two live attenuated vaccines, strains 17D and French neurotropic vaccine (FNV), derived by serial passage of wild-type (WT) strains Asibi and French Viscerotropic virus (FVV), respectively. Both 17D and FNV displayed decreased genetic diversity and resistance to the antiviral Ribavirin compared to their WT parental strains, which are thought to contribute to their attenuated phenotypes. Subsequent studies found that only a few passages of WT strain FVV in HeLa cells resulted in an attenuated virus. In the current study, the genome sequence of FVV following five passages in HeLa cells (FVV HeLa p5) was determined through Next Generation Sequencing (NGS) with the aim to investigate the molecular basis of viral attenuation. It was found that WT FVV and FVV HeLa p5 virus differed by five amino acid substitutions: E-D155A, E-K331R, E-I412V, NS2A-T105A, and NS4B-V98I. Surprisingly, the genetic diversity and Ribavirin resistance of the FVV HeLa p5 virus were not statistically different to WT parent FVV. These findings suggest that while FVV HeLa p5 is attenuated, this is not dependent on a high-fidelity replication complex, characterized by reduced genetic diversity or increased Ribavirin stability, as seen with FNV and 17D vaccines. |
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| format | Article |
| id | doaj.art-2e6cfa9c8acb43029ebc9f3061318b16 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T12:16:34Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
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| series | Viruses |
| spelling | doaj.art-2e6cfa9c8acb43029ebc9f3061318b162023-11-30T22:45:49ZengMDPI AGViruses1999-49152022-03-0114352710.3390/v14030527Genetic Diversity Does Not Contribute to Attenuation of HeLa Passaged Wild-Type Yellow Fever Virus Strain French Viscerotropic VirusAshley E. Strother0Jill K. Thompson1Steven G. Widen2Alan D. T. Barrett3Department of Pathology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USADepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USADepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USADepartment of Pathology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USAThe disease yellow fever was prevented by two live attenuated vaccines, strains 17D and French neurotropic vaccine (FNV), derived by serial passage of wild-type (WT) strains Asibi and French Viscerotropic virus (FVV), respectively. Both 17D and FNV displayed decreased genetic diversity and resistance to the antiviral Ribavirin compared to their WT parental strains, which are thought to contribute to their attenuated phenotypes. Subsequent studies found that only a few passages of WT strain FVV in HeLa cells resulted in an attenuated virus. In the current study, the genome sequence of FVV following five passages in HeLa cells (FVV HeLa p5) was determined through Next Generation Sequencing (NGS) with the aim to investigate the molecular basis of viral attenuation. It was found that WT FVV and FVV HeLa p5 virus differed by five amino acid substitutions: E-D155A, E-K331R, E-I412V, NS2A-T105A, and NS4B-V98I. Surprisingly, the genetic diversity and Ribavirin resistance of the FVV HeLa p5 virus were not statistically different to WT parent FVV. These findings suggest that while FVV HeLa p5 is attenuated, this is not dependent on a high-fidelity replication complex, characterized by reduced genetic diversity or increased Ribavirin stability, as seen with FNV and 17D vaccines.https://www.mdpi.com/1999-4915/14/3/527attenuationflavivirusyellow fever virusgenomegenetic diversity |
| spellingShingle | Ashley E. Strother Jill K. Thompson Steven G. Widen Alan D. T. Barrett Genetic Diversity Does Not Contribute to Attenuation of HeLa Passaged Wild-Type Yellow Fever Virus Strain French Viscerotropic Virus Viruses attenuation flavivirus yellow fever virus genome genetic diversity |
| title | Genetic Diversity Does Not Contribute to Attenuation of HeLa Passaged Wild-Type Yellow Fever Virus Strain French Viscerotropic Virus |
| title_full | Genetic Diversity Does Not Contribute to Attenuation of HeLa Passaged Wild-Type Yellow Fever Virus Strain French Viscerotropic Virus |
| title_fullStr | Genetic Diversity Does Not Contribute to Attenuation of HeLa Passaged Wild-Type Yellow Fever Virus Strain French Viscerotropic Virus |
| title_full_unstemmed | Genetic Diversity Does Not Contribute to Attenuation of HeLa Passaged Wild-Type Yellow Fever Virus Strain French Viscerotropic Virus |
| title_short | Genetic Diversity Does Not Contribute to Attenuation of HeLa Passaged Wild-Type Yellow Fever Virus Strain French Viscerotropic Virus |
| title_sort | genetic diversity does not contribute to attenuation of hela passaged wild type yellow fever virus strain french viscerotropic virus |
| topic | attenuation flavivirus yellow fever virus genome genetic diversity |
| url | https://www.mdpi.com/1999-4915/14/3/527 |
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