TY - JOUR

T1 - Virus adaptation and selection following challenge of animals vaccinated against classical swine fever virus

AU - Fahnøe, Ulrik

AU - Pedersen, Anders Gorm

AU - Johnston, Camille Melissa

AU - Orton, Richard J.

AU - Höper, Dirk

AU - Beer, Martin

AU - Bukh, Jens

AU - Belsham, Graham J.

AU - Rasmussen, Thomas Bruun

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Classical swine fever virus

KW - CSFV

KW - Deep sequencing

KW - Haplotype selection

KW - Vaccination

KW - Viral populations

KW - Virulence

KW - Virus evolution

U2 - 10.3390/v11100932

DO - 10.3390/v11100932

M3 - Journal article

C2 - 31658773

AN - SCOPUS:85074240212

VL - 11

JO - Viruses

JF - Viruses

SN - 1999-4915

IS - 10

M1 - 932

ER -