Limited evolution of the yellow fever virus 17d in a mouse infection model
By infecting mice with the yellow fever virus vaccine strain 17D (YFV-17D; Stamaril®), the dose dependence and evolutionary consequences of neurotropic yellow fever infection was assessed. Highly susceptible AG129 mice were used to allow for a maximal/unlimited expansion of the viral populations. In...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2019.1694394 |
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| author | Dieudonné Buh Kum Niraj Mishra Bram Vrancken Hendrik Jan Thibaut Annelies Wilder-Smith Philippe Lemey Johan Neyts Kai Dallmeier |
| author_facet | Dieudonné Buh Kum Niraj Mishra Bram Vrancken Hendrik Jan Thibaut Annelies Wilder-Smith Philippe Lemey Johan Neyts Kai Dallmeier |
| author_sort | Dieudonné Buh Kum |
| collection | DOAJ |
| description | By infecting mice with the yellow fever virus vaccine strain 17D (YFV-17D; Stamaril®), the dose dependence and evolutionary consequences of neurotropic yellow fever infection was assessed. Highly susceptible AG129 mice were used to allow for a maximal/unlimited expansion of the viral populations. Infected mice uniformly developed neurotropic disease; the virus was isolated from their brains, plaque purified and sequenced. Viral RNA populations were overall rather homogenous [Shannon entropies 0−0.15]. The remaining, yet limited intra-host population diversity (0−11 nucleotide exchanges per genome) appeared to be a consequence of pre-existing clonal heterogeneities (quasispecies) of Stamaril®. In parallel, mice were infected with a molecular clone of YFV-17D which was in vivo launched from a plasmid. Such plasmid-launched YFV-17D had a further reduced and almost clonal evolution. The limited intra-host evolution during unrestricted expansion in a highly susceptible host is relevant for vaccine and drug development against flaviviruses in general. Firstly, a propensity for limited evolution even upon infection with a (very) low inoculum suggests that fractional dosing as implemented in current YF-outbreak control may pose only a limited risk of reversion to pathogenic vaccine-derived virus variants. Secondly, it also largely lowers the chance of antigenic drift and development of resistance to antivirals. |
| format | Article |
| id | doaj-art-e287cfda8a9846fca27134d39da418bd |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-e287cfda8a9846fca27134d39da418bd2025-08-20T01:54:18ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512019-01-01811734174610.1080/22221751.2019.1694394Limited evolution of the yellow fever virus 17d in a mouse infection modelDieudonné Buh Kum0Niraj Mishra1Bram Vrancken2Hendrik Jan Thibaut3Annelies Wilder-Smith4Philippe Lemey5Johan Neyts6Kai Dallmeier7KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, BelgiumKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, BelgiumKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Leuven, BelgiumKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, BelgiumDepartment of Disease Control, London School of Hygiene and Tropical Medicine, London, United KingdomKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Leuven, BelgiumKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, BelgiumKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, BelgiumBy infecting mice with the yellow fever virus vaccine strain 17D (YFV-17D; Stamaril®), the dose dependence and evolutionary consequences of neurotropic yellow fever infection was assessed. Highly susceptible AG129 mice were used to allow for a maximal/unlimited expansion of the viral populations. Infected mice uniformly developed neurotropic disease; the virus was isolated from their brains, plaque purified and sequenced. Viral RNA populations were overall rather homogenous [Shannon entropies 0−0.15]. The remaining, yet limited intra-host population diversity (0−11 nucleotide exchanges per genome) appeared to be a consequence of pre-existing clonal heterogeneities (quasispecies) of Stamaril®. In parallel, mice were infected with a molecular clone of YFV-17D which was in vivo launched from a plasmid. Such plasmid-launched YFV-17D had a further reduced and almost clonal evolution. The limited intra-host evolution during unrestricted expansion in a highly susceptible host is relevant for vaccine and drug development against flaviviruses in general. Firstly, a propensity for limited evolution even upon infection with a (very) low inoculum suggests that fractional dosing as implemented in current YF-outbreak control may pose only a limited risk of reversion to pathogenic vaccine-derived virus variants. Secondly, it also largely lowers the chance of antigenic drift and development of resistance to antivirals.https://www.tandfonline.com/doi/10.1080/22221751.2019.1694394Yellow fever virusvirus diversityfractional dosingYFV-17Dintra-host evolutionlive-attenuated vaccine |
| spellingShingle | Dieudonné Buh Kum Niraj Mishra Bram Vrancken Hendrik Jan Thibaut Annelies Wilder-Smith Philippe Lemey Johan Neyts Kai Dallmeier Limited evolution of the yellow fever virus 17d in a mouse infection model Emerging Microbes and Infections Yellow fever virus virus diversity fractional dosing YFV-17D intra-host evolution live-attenuated vaccine |
| title | Limited evolution of the yellow fever virus 17d in a mouse infection model |
| title_full | Limited evolution of the yellow fever virus 17d in a mouse infection model |
| title_fullStr | Limited evolution of the yellow fever virus 17d in a mouse infection model |
| title_full_unstemmed | Limited evolution of the yellow fever virus 17d in a mouse infection model |
| title_short | Limited evolution of the yellow fever virus 17d in a mouse infection model |
| title_sort | limited evolution of the yellow fever virus 17d in a mouse infection model |
| topic | Yellow fever virus virus diversity fractional dosing YFV-17D intra-host evolution live-attenuated vaccine |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2019.1694394 |
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