The viral BCL2 protein BHRF1 of Epstein-Barr virus promotes AIM2 inflammasome activation to facilitate lytic replication.

ABSTRACT: The absent in melanoma 2 (AIM2) protein recognizes viral and naked dsDNA and recruit apoptosis-associated speck-like protein containing CARD (ASC) to initiate inflammasome activation; however, the subversion of AIM2 activation by Epstein-Barr virus (EBV) infection remains unknown. Here, we reveal that the EBV-encoded viral BCL2 protein BHRF1 promotes AIM2 inflammasome activation. The BHRF1 C-terminal domain binds to AIM2 HIN domain and directly promotes dsDNA recognition and AIM2-ASC interaction, consequently cooperates with viral dsDNA to enable inflammasome activation. The single-site mutations R162A and F164A in BHRF1 and E186A in AIM2 abolish their interaction and AIM2 inflammasome activation. BHRF1 recruits AIM2 inflammasome to the mitochondrial compartment and facilitates EBV lytic r

SUBMITTER: Lan Q 

PROVIDER: S-EPMC12483278 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature