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Open AccessArticle

Virus Adaptation and Selection Following Challenge of Animals Vaccinated against Classical Swine Fever Virus

1
National Veterinary Institute, Technical University of Denmark, Lindholm, DK-4771 Kalvehave, Denmark
2
Department of Health Technology, Section for Bioinformatics, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark
3
Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark
4
Institute of Biodiversity, Animal Health, and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
5
Medical Research Council-University of Glasgow Centre for Virus Research, Institute of Infection, Inflammation and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK
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Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, 17493 Greifswald-Insel Riems, Germany
*
Author to whom correspondence should be addressed.
Present address: Department of Veterinary and Animal Sciences, University of Copenhagen, Grønnegårdsvej 15, DK-1870 Frederiksberg C, Denmark.
Present address: Department of Virus & Microbiological Special Diagnostics, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
Viruses 2019, 11(10), 932; https://doi.org/10.3390/v11100932
Received: 10 September 2019 / Revised: 30 September 2019 / Accepted: 9 October 2019 / Published: 10 October 2019
(This article belongs to the Section Animal Viruses)
Vaccines against classical swine fever have proven very effective in protecting pigs from this deadly disease. However, little is known about how vaccination impacts the selective pressures acting on the classical swine fever virus (CSFV). Here we use high-throughput sequencing of viral genomes to investigate evolutionary changes in virus populations following the challenge of naïve and vaccinated pigs with the highly virulent CSFV strain “Koslov”. The challenge inoculum contained an ensemble of closely related viral sequences, with three major haplotypes being present, termed A, B, and C. After the challenge, the viral haplotype A was preferentially located within the tonsils of naïve animals but was highly prevalent in the sera of all vaccinated animals. We find that the viral population structure in naïve pigs after infection is very similar to that in the original inoculum. In contrast, the viral population in vaccinated pigs, which only underwent transient low-level viremia, displayed several distinct changes including the emergence of 16 unique non-synonymous single nucleotide polymorphisms (SNPs) that were not detectable in the challenge inoculum. Further analysis showed a significant loss of heterogeneity and an increasing positive selection acting on the virus populations in the vaccinated pigs. We conclude that vaccination imposes a strong selective pressure on viruses that subsequently replicate within the vaccinated animal. View Full-Text
Keywords: vaccination; virus evolution; classical swine fever virus; CSFV; virulence; deep sequencing; viral populations; haplotype selection vaccination; virus evolution; classical swine fever virus; CSFV; virulence; deep sequencing; viral populations; haplotype selection
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Fahnøe, U.; Pedersen, A.G.; Johnston, C.M.; Orton, R.J.; Höper, D.; Beer, M.; Bukh, J.; Belsham, G.J.; Rasmussen, T.B. Virus Adaptation and Selection Following Challenge of Animals Vaccinated against Classical Swine Fever Virus. Viruses 2019, 11, 932.

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