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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., Alonso-Lobo, J.M., Montanuy, I., Fischer, C., Sauer, S., Sigal, L., 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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