vPIF-1 is an insulin-like antiferroptotic viral peptide

Belavgeni, Alexia; Maremonti, Francesca; Tonnus, Wulf; Stadtmüller, Marlena; Gavali, Shubhangi; Mallais, Melodie; Flade, Karolin; Brucker, Anne; Becker, Jorunn Naila; Beer, Kristina; Tmava, Mirela; Stumpf, Julian; Gembardt, Florian; Hugo, Christian; Giacca, Mauro; Hale, Benjamin G; Perakakis, Nikolaos; Sha, Wei; Pratt, Derek A; Schally, Andrew V

doi:10.1073/pnas.2300320120

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Belavgeni, A., Maremonti, F., Tonnus, W., Stadtmüller, M., Gavali, S., Mallais, M., Flade, K., Brucker, A., Becker, J. N., Beer, K., Tmava, M., Stumpf, J., Gembardt, F., Hugo, C., Giacca, M., Hale, B. G., Perakakis, N., Sha, W., Pratt, D. A., … Linkermann, A. (2023). vPIF-1 is an insulin-like antiferroptotic viral peptide. Proceedings of the National Academy of Sciences of the United States of America, 120(21), e2300320120. https://doi.org/10.1073/pnas.2300320120

Abstract

Iridoviridae, such as the lymphocystis disease virus-1 (LCDV-1) and other viruses, encode viral insulin-like peptides (VILPs) which are capable of triggering insulin receptors (IRs) and insulin-like growth factor receptors. The homology of VILPs includes highly conserved disulfide bridges. However, the binding affinities to IRs were reported to be 200- to 500-fold less effective compared to the endogenous ligands. We therefore speculated that these peptides also have noninsulin functions. Here, we report that the LCDV-1 VILP can funct