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.
Recommended CitationHernáez, Bruno; Alonso-Lobo, Juan Manuel; Montanuy, Imma; Fischer, Cornelius; Sauer, Sascha; Sigal, Luis J.; Sevilla, Noemí; and Alcamí, Antonio, "A virus-encoded type I interferon decoy receptor enables evasion of host immunity through cell-surface binding." (2018). Department of Microbiology and Immunology Faculty Papers. Paper 101.
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