Iridoviruses secrete insulin-like peptides that compete with the host's own IGF-1, suppressing cell growth signaling to create conditions favorable for viral replication.
Viral mimicryViruses produce insulin-like peptides that hijack host IGF-1 receptor signaling to enhance their own replication
What the researchers found
Viral insulin/IGF-1-like peptides (VILPs) from grouper iridovirus (GIV) are early viral genes that are secreted during infection. Key findings:
- VILPs activate both insulin receptor (IR) and IGF-1 receptor (IGF1R) phosphorylation and the PI3K pathway
- GIV-VILP selectively interacts with IGF1R in a dose- and time-dependent manner
- Paradoxically: IR inhibition suppresses viral replication, while IGF1R inhibition enhances it, and IGF-1 stimulation reduces replication
- VILPs compete with host IGF-1, attenuating IGF1R signaling and reducing cell proliferation
- This viral mimicry mechanism was confirmed in a zebrafish infection model with transcriptome analysis showing negative regulation of cell cycle pathways
Why it matters
This reveals an entirely new strategy viruses use to manipulate their hosts — producing fake insulin-like peptides. Understanding viral peptide mimicry has implications for virology, immunology, and potentially metabolic disease, as these viral peptides could theoretically affect metabolic signaling in infected organisms.
How the study worked
Researchers used grouper iridovirus on grouper and zebrafish cells, characterizing VILP expression timing, secretion, and receptor activation. Receptor-specific inhibitors and IGF-1 stimulation experiments determined the functional effects on viral replication. Transcriptome analysis and a zebrafish in vivo model validated the signaling mechanism.
What this study cannot tell us
The study focused on fish iridoviruses, and it's unknown whether mammalian viruses employ similar insulin-like peptide mimicry strategies. The functional studies were primarily in fish cell lines and zebrafish, limiting direct human health relevance. The precise structural basis for VILPs' selective receptor interactions needs further characterization.
How to read the evidence
This is a rigorous basic science study published in Cell Reports using multiple experimental approaches including in vivo zebrafish models and transcriptomics. The evidence for the mimicry mechanism is strong within the fish virus context studied.
When this study was published
Published in 2025 in Cell Reports, this is a very recent discovery that expands our understanding of how viruses manipulate host peptide signaling.
The bigger picture
The discovery of viral insulin-like peptides challenges the assumption that insulin/IGF signaling is exclusively a host system. If viruses have evolved to produce these mimicry peptides, they may contribute to metabolic disruption during infections. This also opens the door to using VILPs as tools for studying insulin/IGF receptor biology and potentially as templates for novel peptide drug design.
Questions still open
- Do any human-infecting viruses produce similar insulin/IGF-like peptides that could affect metabolic health?
- Could VILPs be engineered as selective IGF1R modulators for therapeutic purposes?
- Does VILP-mediated metabolic disruption contribute to disease severity in viral infections beyond just enhancing replication?
Common questions
How can viruses make insulin-like peptides?
Could viral insulin-like peptides affect human metabolic health?
Read the original research
Viral insulin/IGF-like peptides inhibit IGF-1 receptor signaling to enhance viral replication.
Cell reports, 44(8), 116149
Citation
Chuard, Aurelien; Nesarajah, Kalaimagal; Danazumi, Khadija; Reiners, Kaitlin; Zhang, Fa; Levintov, Lev; Lubos, Marta; Žáková, Lenka; Ruggera, Rachel; McMenamin, Sarah; Vashisth, Harish; Jiráček, Jiří; Dimarchi, Richard; Altindis, Emrah. (2025). Viral insulin/IGF-like peptides inhibit IGF-1 receptor signaling to enhance viral replication.. Cell reports, 44(8), 116149. https://doi.org/10.1016/j.celrep.2025.116149