Human Immune Proteins Show Ancient Antiviral Defense Mechanism Preserved Across Kingdoms
Researchers discovered that human interferon-stimulated genes (ISGs), when expressed in bacteria, can protect against bacteriophage infection — suggesting antiviral defense mechanisms have been conserved across billions of years of evolution. A screen of 306 human ISGs against 11 bacterial viruses showed these human immune proteins can restrict viral replication as effectively as native bacterial defense systems. The findings reveal that one human protein, SPSB1, targets a molecular motif shared by viruses across kingdoms of life, potentially opening new avenues for broad-spectrum antiviral research.
A new preprint study published on bioRxiv demonstrates that human interferon-stimulated genes (ISGs) — proteins activated during viral infection — can function in bacteria to defend against bacteriophages, viruses that infect bacterial cells. In a systematic screen of 306 human ISGs tested against 11 different E. coli phages, the researchers found that several ISGs restricted phage replication with potency comparable to bacteria's own native defense systems. The team then selected for phage mutants that escaped ISG-mediated restriction, which led them to identify the phage DNA primase-helicase complex as a target of the human protein SPSB1. Using X-ray crystallography at 2.0 angstrom resolution, they resolved the structure of the SPSB1-primase complex and identified a short protein sequence motif — DxNxN — present in many viral replication proteins across both animal and bacterial viruses. Further experiments showed that SPSB1 recognizes this motif in human-infecting pathogens including norovirus and poxvirus, triggering their degradation. The study establishes a cross-kingdom experimental framework for studying immune protein function and suggests that some antiviral strategies have remained fundamentally conserved across billions of years of evolution.
What's missing
As a preprint, this study has not yet undergone formal peer review, so findings should be interpreted with caution. The authors do not fully address how broadly the DxNxN motif is distributed across clinically relevant human viruses, nor whether SPSB1 activity against norovirus and poxvirus targets is sufficient to meaningfully reduce infection in vivo. The functional relevance of the bacterial expression system as a true model for human immune responses also remains an open question requiring further validation.
What different sources said
- bioRxivCenter
Human interferon stimulated genes target ancient features of animal and bacterial viral replication
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