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| Nature communications. 2021 Dec 1. doi: 10.1038/s41467-021-27192-w. pii: 10.1038/s41467-021-27192-w |
| Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators. |
| Pennemann FL1, Mussabekova A2, Urban C3, Stukalov A4, Andersen LL5, Grass V6, Lavacca TM7, Holze C8, Oubraham L9, Benamrouche Y10, Girardi E11, Boulos RE12, Hartmann R13, Superti-Furga G14, Habjan M15, Imler JL16, Meignin C17, Pichlmair A18 |
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Abstract The cell intrinsic antiviral response of multicellular organisms developed over millions of years and critically relies on the ability to sense and eliminate viral nucleic acids. Here we use an affinity proteomics approach in evolutionary distant species (human, mouse and fly) to identify proteins that are conserved in their ability to associate with diverse viral nucleic acids. This approach shows a core of orthologous proteins targeting viral genetic material and species-specific interactions. Functional characterization of the influence of 181 candidates on replication of 6 distinct viruses in human cells and flies identifies 128 nucleic acid binding proteins with an impact on virus growth. We identify the family of TAO kinases (TAOK1, -2 and -3) as dsRNA-interacting antiviral proteins and show their requirement for type-I interferon induction. Depletion of TAO kinases in mammals or flies leads to an impaired response to virus infection characterized by a reduced induction of interferon stimulated genes in mammals and impaired expression of srg1 and diedel in flies. Overall, our study shows a larger set of proteins able to mediate the interaction between viral genetic material and host factors than anticipated so far, attesting to the ancestral roots of innate immunity and to the lineage-specific pressures exerted by viruses. |
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© 2021. The Author(s). |
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Publikations ID: 34853303 Quelle: öffnen |
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