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Conservation and variation of the parapoxvirus GM-CSF-inhibitory factor (GIF) proteins

D Deane1, N Ueda2, L M Wise2

  • 1Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, Scotland, UK.

The Journal of General Virology
|March 7, 2009
PubMed

Insights

The pseudocowpox virus GIF protein binds ovine and bovine cytokines, similar to the ORFV GIF protein. However, the bovine papular stomatitis virus GIF protein lacks this cytokine-binding activity.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • The orf virus (ORFV) GIF protein inhibits ovine cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2).
  • A homologous protein has not been identified in other poxvirus genera, prompting an investigation into its conservation within parapoxviruses.

Purpose of the Study:

  • To investigate the conservation and biological activity of GIF proteins in parapoxviruses.
  • To determine if pseudocowpox virus (PCPV) and bovine papular stomatitis virus (BPSV) possess functional GIF proteins homologous to ORFV GIF protein.

Main Methods:

  • Cloning and sequencing of the GIF genes from PCPV and BPSV.
  • Bioinformatic analysis of predicted amino acid sequences, comparing them to ORFV GIF protein.
  • Expression and purification of recombinant PCPV and BPSV GIF proteins.
  • In vitro assays to assess the binding activity of recombinant proteins to ovine and bovine GM-CSF and IL-2.

Main Results:

  • PCPV and BPSV GIF proteins share significant amino acid identity (88% and 37%, respectively) with ORFV GIF protein.
  • Both PCPV and BPSV GIF proteins retain conserved cysteine residues and a WSXWS-like motif essential for ORFV GIF protein activity.
  • Recombinant PCPV GIF protein demonstrated binding to ovine and bovine GM-CSF and IL-2, comparable to ORFV GIF protein.
  • Recombinant BPSV GIF protein exhibited no detectable binding activity to GM-CSF or IL-2.

Conclusions:

  • The GIF protein's cytokine-binding function is conserved in PCPV but not in BPSV.
  • This suggests that the functional conservation of GIF proteins varies within the parapoxvirus genus.
  • Further research is needed to understand the evolutionary trajectory and specific roles of GIF proteins in different poxviruses.

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