Our cells have potent immune sensors that can detect the presence of viral nucleic acid in the cytosol. Unfortunately, almost all viruses utilize a strategy of encapsidation, comprising a protein shell that protects their genomes and impedes them from being sensed or degraded. In our study, we describe how components of innate and adaptive immunity combine to allow the rapid sensing of genomes from incoming viruses. We show that a ubiquitous immune protein called TRIM21 intercepts virions immediately after they enter the cytosol and exposes their genomes to nucleic acid sensors, thereby activating immune transcription pathways before genome replication commences. We demonstrate that TRIM21 enables the RNA sensor RIG-I to detect infection by an incoming RNA virus and the DNA sensor cGAS to detect infection by a DNA virus. By facilitating the sensing of incoming rather than progeny genomes, TRIM21 facilitates a rapid immune response upon infection. In the final part of our manuscript, we illustrate that this system confers an advantage to the host in vivo by demonstrating that there is a rapid TRIM21-dependent inflammatory response in mice upon viral infection, whereas in the absence of TRIM21 production of crucial cytokines like interferon is delayed.
Vyšlo v časopise: TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005253 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005253
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