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Journal of Virology, December 2000, p. 11230-11239, Vol. 74, No. 23
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The Vaccinia Virus Soluble Alpha/Beta Interferon (IFN) Receptor Binds to the Cell Surface and Protects Cells from the Antiviral Effects of IFN

Antonio Alcamí,dagger Julian A. Symons,Dagger and Geoffrey L. Smith*

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom

Received 15 June 2000/Accepted 13 September 2000

Poxviruses encode a broad range of proteins that interfere with host immune functions, such as soluble versions of receptors for the cytokines tumor necrosis factor, interleukin-1beta , gamma interferon (IFN-gamma ), IFN-alpha /beta , and chemokines. These virus-encoded cytokine receptors have a profound effect on virus pathogenesis and enable the study of the role of cytokines in virus infections. The vaccinia virus (VV) Western Reserve gene B18R encodes a secreted protein with 3 immunoglobulin domains that functions as a soluble receptor for IFN-alpha /beta . We have found that after secretion B18R binds to both uninfected and infected cells. The B18R protein present at the cell surface maintains the properties of the soluble receptor, binding IFN-alpha /beta with high affinity and with broad species specificity, and protects cells from the antiviral state induced by IFN-alpha /beta . VV strain Wyeth expressed a truncated B18R protein lacking the C-terminal immunoglobulin domain. This protein binds IFN with lower affinity and retains its ability to bind to cells, indicating that the C-terminal region of B18R contributes to IFN binding. The replication of a VV B18R deletion mutant in tissue culture was restricted in the presence of IFN-alpha , whereas the wild-type virus replicated normally. Binding of soluble recombinant B18R to cells protected the cultures from IFN and allowed VV replication. This represents a novel strategy of virus immune evasion in which secreted IFN-alpha /beta receptors not only bind the soluble cytokine but also bind to uninfected cells and protect them from the antiviral effects of IFN-alpha /beta , maintaining the cells' susceptibility to virus infections. The adaptation of this soluble receptor to block IFN-alpha /beta activity locally will help VV to replicate in the host and spread in tissues. This emphasizes the importance of local effects of IFN-alpha /beta against virus infections.

* Corresponding author. Mailing address: Wright-Fleming Institute, Imperial College School of Medicine, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom. Phone: 44-207-594-3972. Fax: 44-207-594-3973. E-mail: glsmith{at}ic.ac.uk.

dagger Present address: Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom.

Dagger Present address: Department of Viral Diseases, Roche Discovery Welwyn, Welwyn Garden City, Hertfordshire, AL7 3AY, United Kingdom.

Journal of Virology, December 2000, p. 11230-11239, Vol. 74, No. 23
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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