The E3 ubiquitin ligase IDOL suppresses PRRSV replication by targeting viral Nsp3 for SQSTM1-mediated selective autophagic degradation.

IDOL E3 ubiquitin ligase suppresses PRRSV replication by targeting Nsp3 for autophagic degradation, reducing viral replication by over 50% in infected cells.

• Why it matters: PRRSV causes significant economic losses in the swine industry, and understanding host defense mechanisms is crucial for developing effective therapies. The molecular pathways by which the host restricts PRRSV are not fully understood, limiting targeted intervention strategies.
• What they did: Researchers performed transcriptomic analysis of porcine alveolar macrophages from infected piglets, revealing upregulation of IDOL, and validated its antiviral role through in vitro experiments involving overexpression, knockdown, and mutant virus generation.
• The result: IDOL catalyzes K63-linked ubiquitination of Nsp3 at K101, promoting its autophagic degradation via SQSTM1, which suppresses PRRSV replication; mutation at K101 enables viral evasion, highlighting IDOL's potential as a therapeutic target.