This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nazarian, S. H.
Right arrow Articles by McFadden, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nazarian, S. H.
Right arrow Articles by McFadden, G.

 Previous Article  |  Next Article 

Journal of Virology, January 2008, p. 522-528, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.00688-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Yaba Monkey Tumor Virus Encodes a Functional Inhibitor of Interleukin-18{triangledown}

Steven H. Nazarian,1 Masmudur M. Rahman,1,{ddagger} Steven J. Werden,1,{ddagger} Danielle Villeneuve,1 Xiangzhi Meng,2 Craig Brunetti,3 Chalice Valeriano,1 Christina Wong,1 Rajkumari Singh,1 John W. Barrett,1 Yan Xiang,2 and Grant McFadden1*

Biotherapeutics Research Group, Robarts Research Institute and Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada,1 Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229,2 Department of Biology, Trent University, Peterborough, Ontario, Canada3

Received 30 March 2007/ Accepted 17 October 2007

Interleukin-18 (IL-18) is a critical proinflammatory cytokine whose extracellular bioactivity is regulated by a cellular IL-18 binding protein (IL-18BP). Many poxviruses have acquired variants of this IL-18BP gene, some of which have been shown to act as viral virulence factors. Yaba monkey tumor virus (YMTV) encodes a related family member, 14L, which is similar to the orthopoxvirus IL-18BPs. YMTV 14L was expressed from a baculovirus system and tested for its ability to bind and inhibit IL-18. We found that YMTV 14L bound both human IL-18 (hIL-18) and murine IL-18 with high affinity, at 4.1 nM and 6.5 nM, respectively. YMTV 14L was able to fully sequester hIL-18 but could only partially inhibit the biological activity of hIL-18 as measured by gamma interferon secretion from KG-1 cells. Additionally, 17 hIL-18 point mutants were tested by surface plasmon resonance for their ability to bind to YMTV 14L. Two clusters of hIL-18 surface residues were found to be important for the hIL-18-YMTV 14L interaction, in contrast to results for the Variola virus IL-18BP, which has been shown to primarily interact with a single cluster of three amino acids. The altered binding specificity of YMTV 14L most likely represents an adaptation resulting in increased fitness of the virus and affirms the plasticity of poxviral inhibitor domains that target cytokines like IL-18.

* Corresponding author. Present address: University of Florida, 1600 SW Archer Road, ARB Room R4-295, P.O. Box 100332, Gainesville, FL 32610. Phone: (352) 273-6852. Fax: (352) 273-6849. E-mail: grantmcf{at}ufl.edu

{triangledown} Published ahead of print on 24 October 2007.

{ddagger} Present address: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610.

Journal of Virology, January 2008, p. 522-528, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.00688-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»