Glycosylation, Disulfide Bond Formation, and the Presence of a WSXWS-like Motif in the Orf Virus GIF Protein Are Critical for Maintaining the Integrity of Binding to Ovine Granulocyte-macrophage Colony-stimulating Factor and Interleukin-2

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2005 Aug 17

PMID 16103172

Citations 4

Authors

C J McInnes

D Deane

D Haig

A Percival

J Thomson

A R Wood

Affiliations

Soon will be listed here.

Abstract

Orf virus (ORFV), the type species of the family Parapoxviridae, encodes a protein (GIF) that binds and inhibits the ovine cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2). There is no obvious sequence homology between the ORFV protein and any known mammalian GM-CSF- or IL-2-binding proteins. We demonstrate here that many of the biochemical properties of mammalian GM-CSF receptors that are required for efficient binding of GM-CSF are also critical to the GIF protein for binding to ovine GM-CSF (ovGM-CSF). Site-directed mutagenesis of the GIF protein demonstrated, first, the importance of disulfide bonds, and second, that a sequence motif (WDPWV), related to the WSXWS motif of the type 1 cytokine receptor superfamily, was necessary for biological activity. Finally, glycosylation of the GIF protein was also critical for binding to GM-CSF.

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