Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins

J Gen Virol. 2000 May;81(Pt 5):1223-30. doi: 10.1099/0022-1317-81-5-1223.

Abstract

Interleukin-18 (IL-18) is a proinflammatory cytokine that plays a key role in the activation of natural killer and T helper 1 cell responses principally by inducing interferon-gamma (IFN-gamma). Human and mouse secreted IL-18-binding proteins (IL-18BPs) have recently been described which block IL-18 activity but have no sequence similarity to membrane IL-18 receptors. Several poxvirus genes encode proteins with sequence similarity to IL-18BPs. Here we show that vaccinia, ectromelia and cowpox viruses secrete from infected cells a soluble IL-18BP (vIL-18BP) that may modulate the host antiviral response. The ectromelia virus protein was found to block NF-kappaB activation and induction of IFN-gamma in response to IL-18. The highly attenuated vaccinia virus modified virus Ankara encodes IL-18-binding activity, and thus deletion of the vIL-18BP may improve further the safety and immunogenicity of this promising human vaccine candidate. We confirm that molluscum contagiosum virus, a molluscipoxvirus that produces small skin tumours in immunocompetent individuals and opportunistic infections in immunodeficient AIDS patients, also encodes a related, larger vIL-18BP (gene MC54L). This protein may contribute to the lack of inflammatory response characteristic of molluscum contagiosum virus lesions. The expression of vIL-18BPs by distinct poxvirus genera that cause local or general viral dissemination, or persistent or acute infections in the host, emphasizes the importance of IL-18 in response to viral infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Baculoviridae / genetics
  • Cell Line
  • Cowpox virus / genetics
  • Cowpox virus / metabolism
  • Culture Media
  • Ectromelia virus / genetics
  • Ectromelia virus / metabolism
  • Glycoproteins / chemistry
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Molluscum contagiosum virus / genetics
  • Molluscum contagiosum virus / metabolism
  • Orthopoxvirus / genetics*
  • Orthopoxvirus / metabolism*
  • Recombinant Proteins / metabolism
  • Spleen / cytology
  • Spleen / metabolism
  • Vaccinia virus / genetics
  • Vaccinia virus / metabolism

Substances

  • Culture Media
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Recombinant Proteins
  • interleukin-18 binding protein