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Journal of Virology, September 2000, p. 8460-8471, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Expression of Secreted Cytokine and Chemokine Inhibitors by Ectromelia Virus

Vincent P. Smith and Antonio Alcami*

Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom

Received 3 April 2000/Accepted 15 June 2000

The production of secreted proteins that bind cytokines and block their activity has been well characterized as an immune evasion strategy of the orthopoxviruses vaccinia virus (VV) and cowpox virus (CPV). However, very limited information is available on the expression of similar cytokine inhibitors by ectromelia virus (EV), a virulent natural mouse pathogen that causes mousepox. We have characterized the expression and binding properties of three major secreted immunomodulatory activities in 12 EV strains and isolates. Eleven of the 12 EVs expressed a soluble, secreted 35-kDa viral chemokine binding protein with properties similar to those of homologous proteins from VV and CPV. All of the EVs expressed soluble, secreted receptors that bound to mouse, human, and rat tumor necrosis factor alpha. We also detected the expression of a soluble, secreted interleukin-1beta (IL-1beta ) receptor (vIL-1beta R) by all of the EVs. EV differed from VV and CPV in that binding of human 125I-IL-1beta to the EV vIL-1beta R could not be detected. Nevertheless, the EV vIL-1beta R prevented the interaction of human and mouse IL-1beta with cellular receptors. There are significant differences in amino acid sequence between the EV vIL-1beta R and its VV and CPV homologs which may account for the results of the binding studies. The conservation of these activities in EV suggests evolutionary pressure to maintain them in a natural poxvirus infection. Mousepox represents a useful model for the study of poxvirus pathogenesis and immune evasion. These findings will facilitate future study of the role of EV immunomodulatory factors in the pathogenesis of mousepox.

* Corresponding author. Mailing address: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QP, United Kingdom. Phone: 44 (1223) 336922. Fax: 44 (1223) 336926. E-mail: aa258{at}mole.bio.cam.ac.uk.

Journal of Virology, September 2000, p. 8460-8471, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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