PRRSV NSP5 orchestrates dual immune disruption by targeting NLRP3 and STING.

ABSTRACT: Inflammasomes and interferons are two critical defense mechanisms of innate immunity, and their imbalance is a key strategy employed by viruses to evade host immune surveillance. During porcine reproductive and respiratory syndrome virus (PRRSV) infection, an arteritis virus, a characteristic "high inflammation, low interferon" immune imbalance is observed. This study identifies PRRSV non-structural protein NSP5 as a central mediator of this immune imbalance. We demonstrate that NSP5 recruits NLRP3 to the endoplasmic reticulum (ER)-mitochondrial interface, triggering ER stress and Ca²⁺ leakage, which subsequently activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome. Notably, a specific NSP5 mutation (G30A) abolishes its ability to activate NLRP3. PRRSV carryin

SUBMITTER: Huang X 

PROVIDER: S-EPMC12533338 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature