Viral insulin-like peptides activate human insulin and IGF-1 receptor signaling: A paradigm shift for host–microbe interactions

Significance Although there has been tremendous progress in understanding hormone action and its relationship to human physiology and disease, there has been no comprehensive approach to search the viral genome for the presence of human-like hormones. Here, using a bioinformatics approach, we have identified 16 different human peptide hormones/growth factors, including four insulin/insulin growth factor (IGF)1-like peptides (VILPs) that have homologous sequences in viruses. When these VILPs were chemically synthesized, the resulting peptides could bind to human and murine insulin and IGF1 receptors, stimulate postreceptor signaling, increase glucose uptake, and activate proliferation of cells. Injection of VILPs into mice can significantly lower the blood glucose. Thus, VILPs are members of the insulin superfamily and first characterized viral hormones.