Self-guarding of MORC3 enables virulence factor-triggered immunity.

ABSTRACT: Pathogens use virulence factors to inhibit the immune system¹. The guard hypothesis^2,3 postulates that hosts monitor (or 'guard') critical innate immune pathways such that their disruption by virulence factors provokes a secondary immune response¹. Here we describe a 'self-guarded' immune pathway in human monocytes, in which guarding and guarded functions are combined in one protein. We find that this pathway is triggered by ICP0, a key virulence factor of herpes simplex virus type 1, resulting in robust induction of anti-viral type I interferon (IFN). Notably, induction of IFN by ICP0 is independent of canonical immune pathways and the IRF3 and IRF7 transcription factors. A CRISPR screen identified the ICP0 target MORC3⁴ as an essential negative

SUBMITTER: Gaidt MM 

PROVIDER: S-EPMC9045311 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature