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Journal of Virology, September 2009, p. 9602-9607, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.01078-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Inhibition of Macrophage Activation by the Myxoma Virus M141 Protein (vCD200){triangledown}

Leiliang Zhang,1 Marianne Stanford,2 Jia Liu,1 Catherine Barrett,2 Lei Jiang,3 A. Neil Barclay,3 and Grant McFadden1,2*

Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida 32610,1 Robarts Research Institute and Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada N6G 2V4,2 Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom3

Received 27 May 2009/ Accepted 25 June 2009

The M141 protein of myxoma virus (MYXV) is a viral CD200 homolog (also called vOX-2) that inhibits macrophage activation in infected rabbits. Here, we show that murine myeloid RAW 264.7 cells became activated when infected with MYXV in which the M141 gene was deleted (vMyx-M141KO) but not with the parental wild-type MYXV. Moreover, transcript and protein levels of tumor necrosis factor and granulocyte colony-stimulating factor were rapidly upregulated in an NF-{kappa}B-dependent fashion in the RAW 264.7 cells infected with vMyx-M141KO. M141 protein is present in the virion and counteracts this NF-{kappa}B activation pathway upon infection with the wild-type MYXV. Our data suggest that upregulation of these classic macrophage-related proinflammatory cytokine markers following infection of myeloid cells with the M141-knockout MYXV is mediated via the rapid activation of the cellular NF-{kappa}B pathway.


* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610. Phone: (352) 273-6852. Fax: (352) 273-6849. E-mail: grantmcf{at}ufl.edu

{triangledown} Published ahead of print on 1 July 2009.


Journal of Virology, September 2009, p. 9602-9607, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.01078-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.