Type I interferons (IFNs) are cytokines that are used clinically as antiviral and antitumour agents. The interaction of IFNs with their heterodimeric type I IFN receptor comprised of IFNAR1 and IFNAR2 is a first step to inducing biological actions. Here, we describe the successful mimicry of IFN-β by a peptide isolated by phage-display screening using a neutralizing anti-IFN-β monoclonal antibody. The 15-mer peptide, designated SYR6, was shown to compete with IFN-β for binding to type I IFN receptor in a concentration-dependent manner, and was shown to elicit antiviral activity on cultured cells. This antiviral activity was not eliminated in the presence of neutralizing monoclonal antibodies to IFN-α, -β and -γ, and a low concentration of soluble type I IFN receptor, suggesting that it was not due to IFN contamination or the induction of endogenous IFNs by SYR6. This peptide might be a potent agonist to provide a mechanism of activating heterodimeric cytokine receptors.

Abbreviations used: ECD, extracellular domain; IFN, interferon; mAb, monoclonal antibody; sIFNR, soluble human IFN receptor; SV, sindbis virus; VSV, vesicular stomatitis virus.

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Author notes

The nucleotide sequence of phage 6 has been deposited in the DDBJ, EMBL and GenBank Nucleotide Sequence Databases under accession no. AB058940.