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

Alshad S. Lalani, Traci L. Ness, Rajkumari Singh, Jeffrey K. Harrison, Bruce T. Seet, David J. Kelvin, Grant McFadden, Richard W. Moyer

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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 (K(i) = 0.07-1.02 nM). These proteins also displayed similar abilities to inhibit (IC50 = 6.3- 10.5 nM) human macrophage inflammatory protein-1α-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.

Original languageEnglish (US)
Pages (from-to)173-184
Number of pages12
JournalVirology
Volume250
Issue number1
DOIs
StatePublished - Oct 10 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Virology

Cite this

Lalani, A. S., Ness, T. L., Singh, R., Harrison, J. K., Seet, B. T., Kelvin, D. J., McFadden, G., & Moyer, R. W. (1998). Functional comparisons among members of the poxvirus T1/35kDa family of soluble CC-chemokine inhibitor glycoproteins. Virology, 250(1), 173-184. https://doi.org/10.1006/viro.1998.9340