Pathogen-driven CRISPR screens identify TREX1 as a regulator of DNA self-sensing during influenza virus infection.

ABSTRACT: Host:pathogen interactions dictate the outcome of infection, yet the limitations of current approaches leave large regions of this interface unexplored. Here, we develop a novel fitness-based screen that queries factors important during the middle to late stages of infection. This is achieved by engineering influenza virus to direct the screen by programming dCas9 to modulate host gene expression. Our genome-wide screen for pro-viral factors identifies the cytoplasmic DNA exonuclease TREX1. TREX1 degrades cytoplasmic DNA to prevent inappropriate innate immune activation by self-DNA. We reveal that this same process aids influenza virus replication. Infection triggers release of mitochondrial DNA into the cytoplasm, activating antiviral signaling via cGAS and STING. TREX1 metabolizes the DN

SUBMITTER: King CR 

PROVIDER: S-EPMC10528757 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature