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Orf virus encodes a novel secreted protein inhibitor of granulocyte-macrophage colony-stimulating factor and

D Deane1, C J McInnes, A Percival

  • 1Moredun Research Institute, International Research Centre, Penicuik, Scotland.

Journal of Virology
|January 11, 2000
PubMed

Insights

Orf virus produces a novel protein that inhibits ovine granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2). This finding highlights the importance of these cytokines in antiviral immunity during orf virus infection.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Orf virus (ORFV) is a parapoxvirus known to infect sheep and goats, and occasionally humans.
  • Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) are critical cytokines in orchestrating immune responses, particularly antiviral immunity.

Purpose of the Study:

  • To identify and characterize novel viral factors involved in modulating host immune responses during orf virus infection.
  • To investigate the interaction of the identified viral factor with ovine and human cytokines.

Main Methods:

  • Gene expression analysis of orf virus-infected cells.
  • Protein purification and characterization, including oligomerization studies.
  • Biochemical assays to determine binding affinity (K(d)) to ovine and human GM-CSF and IL-2.
  • Detection of the viral factor in lymph fluid from infected animals.

Main Results:

  • A novel gene, GM-CSF- and IL-2-inhibitory factor (GIF), was identified and expressed as an intermediate-late viral gene.
  • GIF forms homodimers and tetramers and binds ovine GM-CSF (K(d) = 369 pM) and ovine IL-2 (K(d) = 1.04 nM) with high affinity.
  • GIF does not bind human GM-CSF or IL-2, despite ORFV being a zoonotic pathogen.
  • GIF was detected in lymph draining the infection site and correlated with reduced GM-CSF levels.

Conclusions:

  • Orf virus encodes a specific inhibitor (GIF) targeting key ovine immune cytokines, GM-CSF and IL-2.
  • The selective inhibition of ovine cytokines suggests a mechanism for viral immune evasion.
  • The findings underscore the crucial role of GM-CSF and IL-2 in host antiviral immunity against orf virus.

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