Human Immune Proteins Show Ancient Antiviral Defense Mechanism Preserved Across Kingdoms
Researchers discovered that human interferon-stimulated genes (ISGs) can protect bacteria against bacteriophage infection, revealing antiviral mechanisms conserved across billions of years of evolution. A screen of 306 human ISGs against 11 bacterial viruses showed these immune proteins can restrict viral replication as effectively as native bacterial defenses, and identified the protein SPSB1 as targeting a specific molecular motif found in both bacterial and animal viruses. This finding suggests human antiviral immunity is built on ancient, broadly conserved principles and opens a new cross-kingdom method for studying immune function.
A new study published on bioRxiv demonstrates that human interferon-stimulated genes (ISGs) — proteins activated during viral infection — retain functional antiviral activity even when expressed in bacteria, protecting against diverse bacteriophages. In a systematic screen of 306 human ISGs tested against 11 different E. coli bacteriophages, the researchers found that several ISGs could restrict phage replication with potency comparable to bacteria's own native defense systems. By selecting for phage mutants that escaped ISG-mediated restriction, the team identified the phage DNA primase-helicase complex as a target of the human protein SPSB1. A high-resolution 2.0 angstrom crystal structure of the SPSB1-primase complex revealed that SPSB1 recognizes a short protein sequence motif — DxNxN — present in replication proteins of many animal and bacterial viruses. The researchers further showed that SPSB1 recognizes and triggers degradation of proteins bearing this motif from human pathogens including norovirus and poxvirus, suggesting broad antiviral relevance. These findings indicate that human antiviral immunity targets molecular features of viral replication that have been conserved across kingdoms of life for billions of years, and establish bacteria as a practical experimental platform for dissecting the function of poorly characterized human immune genes.
What's missing
As a preprint, this study has not yet undergone formal peer review, so findings should be interpreted with caution. The study does not fully address whether the DxNxN motif is present in all major human viral pathogens or how frequently viruses mutate this motif to escape SPSB1 restriction in vivo. The in vivo relevance of SPSB1-mediated restriction during actual human infections with norovirus or poxvirus remains to be demonstrated in animal models or clinical data. Additionally, the bacterial expression system may not fully recapitulate the regulatory environment of human cells.
What different sources said
- bioRxivCenter
Human interferon stimulated genes target ancient features of animal and bacterial viral replication
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