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, Douglas McFadden, Richard W. Moyer

Research output: Contribution to journalArticle

57 Citations (Scopus)

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

Fingerprint

Poxviridae
CC Chemokines
Glycoproteins
Leporipoxvirus
Orthopoxvirus
Proteins
Aptitude
Vaccinia virus
Chemotaxis
Myxoma virus
Calcium
Macrophage Inflammatory Proteins
Chemokine Receptors
Viral Proteins
Interleukin-8
Inhibitory Concentration 50
Monocytes
Carrier Proteins
Neutrophils
Cytokines

ASJC Scopus subject areas

  • Virology

Cite this

Lalani, A. S., Ness, T. L., Singh, R., Harrison, J. K., Seet, B. T., Kelvin, D. J., ... 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

Functional comparisons among members of the poxvirus T1/35kDa family of soluble CC-chemokine inhibitor glycoproteins. / Lalani, Alshad S.; Ness, Traci L.; Singh, Rajkumari; Harrison, Jeffrey K.; Seet, Bruce T.; Kelvin, David J.; McFadden, Douglas; Moyer, Richard W.

In: Virology, Vol. 250, No. 1, 10.10.1998, p. 173-184.

Research output: Contribution to journalArticle

Lalani, AS, Ness, TL, Singh, R, Harrison, JK, Seet, BT, Kelvin, DJ, McFadden, D & Moyer, RW 1998, 'Functional comparisons among members of the poxvirus T1/35kDa family of soluble CC-chemokine inhibitor glycoproteins', Virology, vol. 250, no. 1, pp. 173-184. https://doi.org/10.1006/viro.1998.9340
Lalani, Alshad S. ; Ness, Traci L. ; Singh, Rajkumari ; Harrison, Jeffrey K. ; Seet, Bruce T. ; Kelvin, David J. ; McFadden, Douglas ; Moyer, Richard W. / Functional comparisons among members of the poxvirus T1/35kDa family of soluble CC-chemokine inhibitor glycoproteins. In: Virology. 1998 ; Vol. 250, No. 1. pp. 173-184.
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