Cross-species analysis of viral nucleic acid interactors identifies TAOKs as immune regulators

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 used 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 revealed a conserved core of proteins targeting viral genetic material and species-specific interactants. Functional characterization of the influence of 181 candidates on replication of 6 distinct viruses in human cells and flies identified 128 nucleic acid binding proteins with an impact on virus growth. We identified the family of TAO kinases (TAOK1, -2 and -3) as dsRNA-interacting antiviral proteins and show their requirement in type-I interferon induction. Depletion of TAO kinases in mammals or flies led 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 reveals a by far larger interaction space 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Christian Urban  

LAB HEAD: Andreas Pichlmair

PROVIDER: PXD027919 | Pride | 2021-09-22

REPOSITORIES: Pride