{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T12:39:05Z","timestamp":1769517545053,"version":"3.49.0"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T00:00:00Z","timestamp":1570665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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 na\u00efve and vaccinated pigs with the highly virulent CSFV strain \u201cKoslov\u201d. 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 na\u00efve animals but was highly prevalent in the sera of all vaccinated animals. We find that the viral population structure in na\u00efve 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.<\/jats:p>","DOI":"10.3390\/v11100932","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T03:07:11Z","timestamp":1570763231000},"page":"932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Virus Adaptation and Selection Following Challenge of Animals Vaccinated against Classical Swine Fever Virus"],"prefix":"10.3390","volume":"11","author":[{"given":"Ulrik","family":"Fahn\u00f8e","sequence":"first","affiliation":[{"name":"National Veterinary Institute, Technical University of Denmark, Lindholm, DK-4771 Kalvehave, Denmark"},{"name":"Department of Health Technology, Section for Bioinformatics, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark"},{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9650-8965","authenticated-orcid":false,"given":"Anders Gorm","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Health Technology, Section for Bioinformatics, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1550-2666","authenticated-orcid":false,"given":"Camille Melissa","family":"Johnston","sequence":"additional","affiliation":[{"name":"National Veterinary Institute, Technical University of Denmark, Lindholm, DK-4771 Kalvehave, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3389-4325","authenticated-orcid":false,"given":"Richard J.","family":"Orton","sequence":"additional","affiliation":[{"name":"Institute of Biodiversity, Animal Health, and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK"},{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8408-2274","authenticated-orcid":false,"given":"Dirk","family":"H\u00f6per","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Beer","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7815-4806","authenticated-orcid":false,"given":"Jens","family":"Bukh","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1187-4873","authenticated-orcid":false,"given":"Graham J.","family":"Belsham","sequence":"additional","affiliation":[{"name":"National Veterinary Institute, Technical University of Denmark, Lindholm, DK-4771 Kalvehave, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4241-1559","authenticated-orcid":false,"given":"Thomas Bruun","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"National Veterinary Institute, Technical University of Denmark, Lindholm, DK-4771 Kalvehave, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4171","DOI":"10.1073\/pnas.90.9.4171","article-title":"Rates of spontaneous mutation among RNA viruses","volume":"90","author":"Drake","year":"1993","journal-title":"Proc. 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