Virus adaptation and selection following challenge of animals vaccinated against classical swine fever virus

Fahnøe, U., Pedersen, A. G., Johnston, C. M., Orton, R. J. , Höper, D., Beer, M., Bukh, J., Belsham, G. J. and Rasmussen, T. B. (2019) Virus adaptation and selection following challenge of animals vaccinated against classical swine fever virus. Viruses, 11(10), e932. (doi: 10.3390/v11100932)

Abstract

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.

• Item Type: Articles
• Additional Information: This study was supported by the Danish Research Council for Technology and Production Sciences [DRCTPS grant 274-07-0198] and by internal resources from the National Veterinary Institute within the Technical University of Denmark. Furthermore, the work was supported by the European project Epi-SEQ (research project supported under the 2nd Joint Call for Transnational Research Projects by EMIDA ERA-NET [FP7 project no. 219235]) and by the German Federal Ministry for Education and Research [BMBF, grant 01KI1016A]. In addition, the study was supported by funding from the Independent Research Fund Denmark [4004-00598] and the Danish Cancer Society [R204-A12639].
• Keywords: Vaccination, virus evolution, classical swine fever virus, CSFV, virulence, deep sequencing, viral populations, haplotype selection.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Orton, Dr Richard

Creator Roles

Orton, R. J.: Formal analysis, Writing – original draft, Writing – review and editing

• Authors: Fahnøe, U., Pedersen, A. G., Johnston, C. M., Orton, R. J., Höper, D., Beer, M., Bukh, J., Belsham, G. J., and Rasmussen, T. B.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Viruses
• Publisher: MDPI
• ISSN: 1999-4915
• ISSN (Online): 1999-4915
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Viruses 11(10):e932
• Publisher Policy: Reproduced under a Creative Commons License