Orf virus ORFV112, ORFV117 and ORFV127 contribute to ORFV IA82 virulence in sheep

Vet Microbiol. 2021 Jun:257:109066. doi: 10.1016/j.vetmic.2021.109066. Epub 2021 Apr 10.

Abstract

The parapoxvirus orf virus (ORFV) encodes several immunomodulatory proteins (IMPs) that modulate host innate and pro-inflammatory responses to infection. Using the ORFV IA82 strain as the parental virus, recombinant viruses with individual deletions in the genes encoding the IMPs chemokine binding protein (CBP; ORFV112), inhibitor of granulocyte-monocyte colony-stimulating factor and IL-2 (GIF, ORFV117) and interleukin 10 homologue (vIL-10; ORFV127) were generated and characterized in vitro and in vivo. The replication properties of the individual gene deletion viruses in cell culture was not affected comparing with the parental virus. To investigate the effect of the individual gene deletions in ORFV infection and pathogenesis, groups of four lambs were inoculated with each virus and were monitored thereafter. Lambs inoculated with either recombinant or with the parental ORFV developed characteristic lesions of contagious ecthyma. The onset, nature and severity of the lesions in the oral commissure were similar in all inoculated groups from the onset (3 days post-inoculation [pi]) to the peak of clinical lesions (days 11-13 pi). Nonetheless, from days 11-13 pi onwards, the oral lesions in lambs inoculated with the recombinant viruses regressed faster than the lesions produced by the parental virus. Similarly, the amount of virus shed in the lesions were equivalent among lambs of all groups up to day 15 pi, yet they were significantly higher in the parental virus group from day 16-21 pi. In conclusion, individual deletion of these IMP genes from the ORFV genome resulted in slight reduction in virulence in vivo, as evidenced by a reduction in the duration of the clinical disease and virus shedding.

Keywords: Orf virus; Pathogenesis; Recombinant virus; Virulence.

MeSH terms

  • Age Factors
  • Animals
  • Cytokines / genetics
  • Cytokines / immunology
  • Ecthyma, Contagious / immunology
  • Ecthyma, Contagious / virology
  • Genes, Viral / immunology*
  • Genome, Viral
  • Mutation
  • Orf virus / genetics*
  • Orf virus / immunology
  • Orf virus / pathogenicity*
  • Sheep / virology
  • Sheep Diseases / immunology
  • Sheep Diseases / virology*
  • Signal Transduction
  • Virulence
  • Virus Replication / genetics
  • Virus Shedding
  • Whole Genome Sequencing

Substances

  • Cytokines