BRLF1 suppresses RNA Pol III-mediated RIG-I inflammasome activation in the early EBV lytic lifecycle

ABSTRACT: Latent infection with herpesviruses constitutively activates inflammasomes, while lytic replication suppresses their activation through distinct mechanisms. However, how EBV lytic replication inhibits the activation of inflammasomes remains unknown. Here, we reveal that BRLF1 inhibits inflammasome activation and BRLF1 deficiency significantly increases the activation of inflammasomes and pyroptosis during early lytic lifecycle. BRLF1 interacts with the RNA polymerase III subunits to suppress immunostimulatory small RNA transcription, RIG-I inflammasome activation and antiviral responses. Consequently, BRLF1-deficient EBV primary infection induces robust T cell and NK cell activation and killing through IL-1? and IL-18. A BRLF1-derived peptide that inhibits inflammasome activation is suffic

SUBMITTER: Mr. Xubing Long 

PROVIDER: S-SCDT-EMBOR-2020-50714V1 | biostudies-other |

REPOSITORIES: biostudies-other