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A virus-encoded type I interferon decoy receptor enables evasion of host immunity through cell-surface binding

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Item Type:Article
Title:A virus-encoded type I interferon decoy receptor enables evasion of host immunity through cell-surface binding
Creators Name:Hernáez, B. and Alonso-Lobo, J.M. and Montanuy, I. and Fischer, C. and Sauer, S. and Sigal, L. and Sevilla, N. and Alcamí, A.
Abstract:Soluble cytokine decoy receptors are potent immune modulatory reagents with therapeutic applications. Some virus-encoded secreted cytokine receptors interact with glycosaminoglycans expressed at the cell surface, but the biological significance of this activity in vivo is poorly understood. Here, we show the type I interferon binding protein (IFNα/βBP) encoded by vaccinia and ectromelia viruses requires of this cell binding activity to confer full virulence to these viruses and to retain immunomodulatory activity. Expression of a variant form of the IFNα/βBP that inhibits IFN activity, but does not interact with cell surface glycosaminoglycans, results in highly attenuated viruses with a virulence similar to that of the IFNα/βBP deletion mutant viruses. Transcriptomics analysis and infection of IFN receptor-deficient mice confirmed that the control of IFN activity is the main function of the IFNα/βBP in vivo. We propose that retention of secreted cytokine receptors at the cell surface may largely enhance their immunomodulatory activity.
Keywords:Glycosaminoglycans, HeLa Cells, Inbred BALB C Mice, Interferon Type I, Poxviridae, Poxviridae Infections, Vero Cells, Viral Proteins, Virus Attachment, Animals, Cercopithecus aethiops, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:9
Number:1
Page Range:5440
Date:21 December 2018
Official Publication:https://doi.org/10.1038/s41467-018-07772-z
PubMed:View item in PubMed

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