期刊
VIRUSES-BASEL
卷 11, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/v11100932
关键词
vaccination; virus evolution; classical swine fever virus; CSFV; virulence; deep sequencing; viral populations; haplotype selection
类别
资金
- Danish Research Council for Technology and Production Sciences [DRCTPS] [274-07-0198]
- European project Epi-SEQ (2nd Joint Call for Transnational Research Projects by EMIDA ERA-NET [FP7 project]) [219235]
- German Federal Ministry for Education and Research [BMBF] [01KI1016A]
- Independent Research Fund Denmark [4004-00598]
- Danish Cancer Society [R204-A12639]
- MRC [MC_UU_12014/12] Funding Source: UKRI
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 naive 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 naive animals but was highly prevalent in the sera of all vaccinated animals. We find that the viral population structure in naive 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.
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