Summary

Orf virus (ORFV) is the prototype species of the genus Parapoxvirus, a member of the Poxviridae family that causes contagious ecthyma in sheep, goats and, occasionally, humans. The virus is characterised by a linear double-stranded DNA genome of approximately 138–140 kilobase pairs, encoding a complement of core poxvirus genes alongside unique factors that facilitate replication in the specialised immune environment of the skin epidermis. ORFV entry into keratinocytes and dermal fibroblasts triggers a cascade of viral gene expression entirely within the host cytoplasm, orchestrated by a virus-encoded multisubunit DNA-dependent RNA polymerase. The interplay between viral immunomodulatory proteins—such as those mimicking host interleukin-10 or vascular endothelial growth factor—and host immune defences governs lesion formation, viral spread and resolution. Infection dynamics are shaped by viral factors that dampen innate responses, recruit target cells and block apoptosis, as well as by host clearance mechanisms involving neutralising antibodies, cytotoxic T cells and skin-resident memory cells. Global epidemiological studies underscore the zoonotic potential of ORFV, which maintains a perennial presence in pastoral regions and poses challenges for animal health, trade and rural livelihoods. Advances in genome sequencing and reverse genetics have illuminated the evolutionary origins of key virulence genes, demonstrating capture of host genes and expansion of signalling inhibitors. Understanding the biology and pathogenesis of ORFV provides a foundation for improved diagnostics, targeted antivirals and more effective vaccination strategies in both veterinary and human contexts.

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Orf Virus Biology and Infection Dynamics publication trend

The graph below shows the total number of articles in orf virus biology and infection dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Parapoxvirus: A genus of poxviruses characterised by ovoid virions and a high G + C content that includes orf virus as its prototype species.

vRNAP: Viral RNA polymerase, a multisubunit complex encoded by poxviruses that drives transcription of viral genes within the host cytoplasm.

Heterologous prime–boost: A vaccination strategy that uses different delivery platforms (e.g., DNA followed by protein) to enhance the magnitude and quality of the immune response.

Cytokine storm: A dysregulated and excessive release of inflammatory mediators, which can result from co-infection and contribute to tissue damage.

References

  1. Orf virus DNA prime-protein boost strategy is superior to adenovirus-based vaccination in mice and sheep. Frontiers in Immunology (2023).
  2. The cooperation between orf virus and Staphylococcus aureus leads to intractable lesions in skin infection. Frontiers in Cellular and Infection Microbiology (2024).
  3. Genistein is effective in inhibiting Orf virus infection in vitro by targeting viral RNA polymerase subunit RPO30 protein. Frontiers in Microbiology (2024).
  4. Molecular Genetic Analysis of Orf Virus: A Poxvirus That Has Adapted to Skin. Viruses (2015).

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