Functional comparisons among members of the poxvirus T1/35kDa family of soluble CC-chemokine inhibitor glycoproteins

Virology. 1998 Oct 10;250(1):173-84. doi: 10.1006/viro.1998.9340.

Abstract

Many poxviruses express a 35-40-kDa secreted protein, termed "T1" (for leporipoxviruses) or "35kDa" (for orthopoxviruses), that binds CC-chemokines with high affinity but is unrelated to any known cellular proteins. Many previously identified poxvirus cytokine-binding proteins display strict species ligand-binding specificity. Because the T1 and 35kDa proteins share only 40% amino acid identity, we compared the abilities of purified myxoma virus-T1 (M-T1) and vaccinia virus (strain Lister)- and rabbitpox virus-35kDa proteins to inhibit human CC-chemokines in vitro. All three proteins were equally effective in preventing several human CC-chemokines from binding to target chemokine receptors and blocking subsequent intracellular calcium release. The inhibitory affinities were comparable (Ki = 0.07-1.02 nM). These proteins also displayed similar abilities to inhibit (IC50 = 6.3-10.5 nM) human macrophage inflammatory protein-1alpha-mediated chemotaxis of human monocytes. None of the viral proteins blocked interleukin-8-mediated calcium flux or chemotaxis of human neutrophils, confirming that the biological specificity of the T1/35kDa family is targeted inhibition of CC-chemokines. Despite the significant sequence divergence between the leporipoxvirus T1 and orthopoxvirus 35kDa proteins, our data suggest that their CC-chemokine binding and inhibitory properties appear to be species nonspecific and that the critical motifs most likely reside within the limited regions of conservation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium / metabolism
  • Chemokines / metabolism*
  • Chemotaxis, Leukocyte
  • Glycoproteins / chemistry
  • Glycoproteins / isolation & purification
  • Glycoproteins / metabolism
  • Glycosylation
  • HL-60 Cells
  • Humans
  • Molecular Weight
  • Monocytes / cytology
  • Myxoma virus / immunology*
  • Neutrophils / cytology
  • Receptors, Chemokine
  • Sequence Analysis
  • Tumor Cells, Cultured
  • Vaccinia virus / immunology*
  • Viral Proteins / chemistry
  • Viral Proteins / isolation & purification
  • Viral Proteins / metabolism*

Substances

  • Chemokines
  • Glycoproteins
  • Receptors, Chemokine
  • Viral Proteins
  • Calcium