Editors' ChoiceMicrobiome

Don’t forget about me! Viral-host metabolic interactions in the microbiome

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Science Translational Medicine  21 Mar 2018:
Vol. 10, Issue 433, eaat1641
DOI: 10.1126/scitranslmed.aat1641


Viruses present in the human microbiome produce peptides homologous to human insulin/insulin-like growth factors that may influence host metabolic pathways.

The human microbiome is a complex ecosystem whose functions are believed to be important to host metabolism. Although our understanding of bacterial-host metabolic interactions grows, we know little about whether other microbiome constituents, such as viruses, archaea, or fungi, also regulate metabolic functions. In a recent article by Altindis et al., the authors demonstrate that viral insulin-like peptides (VILPs) are able to interact with host insulin and insulin-like growth factor (IGF) receptors in the same manner as structurally related endogenous hormones. Building on studies that identified homologous viral and human proteins, the authors searched the NCBI database for viral sequences with homology to human peptide hormones. This search identified viral peptides with significant homology to insulin/IGF, inhibin, fibroblast growth factor, adipsin, and endothelin. Human and viral insulin/IGF protein sequences were found to have the greatest sequence similarity and predicted structural similarly. The authors then synthesized VILPs and demonstrated biologic activity with activation of insulin/IGF receptors in vitro and lowering of blood glucose in mice. Interestingly, the authors were able to identify sequences that encode VILPs in viral DNA isolated from patient stool samples suggesting that VILPs may be part of the human microbiome. This study lays the foundation for how researchers might understand the interaction between viral constituents of the human microbiome and host metabolism in homeostasis or disease. VILPs might also serve as a foundation for novel therapies to treat metabolic diseases. It remains to be seen how the presence of VILP sequences in the microbiome would translate to functions in vivo; future studies are needed to understand the native physiology of VILPs and better define the viral constituents of the microbiome. It will also be interesting to see whether other viral peptides identified in this study with homology to human hormones can facilitate host-viral interactions and further establish the importance of viruses as an active component of the microbiome.

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