Viral subversion of the host ubiquitin proteasome system is broadly sensed by the NLRP1 inflammasome

NSP1 from simian rotavirus SA11 potently activates human NLRP1, with NLRP1 subverting NSP1 E3 ligase activity to trigger N-terminal degradation and inflammasome activation.

• Why it matters: Viral protease and other virulence activities can be sensed by NLRP1, but whether viral subversion of the ubiquitin proteasome system is a common trigger was unclear.
• What they did: The study screened 81 viral E3 ligases and E3 ligase adaptor proteins for human NLRP1 activation, then tested NSP1 expressed ectopically or during infection and extended findings across mammalian NLRP1 orthologs.
• The result: Recognition of viral E3 ligase activity is broadly conserved across mammalian NLRP1 orthologs but is highly species- and virus-specific, supporting viral E3 ligase activity as a conserved NLRP1 trigger.