Nsp2 replicase-mediated viral uncoating in porcine alveolar macrophages contributes to the attenuation of PRRSV-2 live attenuated vaccine.

ABSTRACT: Type 2 porcine reproductive and respiratory syndrome virus (PRRSV-2) poses a major threat to global swine production. While live attenuated vaccines (LAVs) remain the most effective countermeasure, the molecular mechanisms underlying PRRSV-2 attenuation remain enigmatic. Here, we reveal that PRRSV-2 LAVs exhibit impaired replication in their primary cellular targets-porcine alveolar macrophages (PAMs), with viral uncoating defects being the critical replication barrier. Mechanistically, we identified nonstructural protein 2 (nsp2) as the key viral determinant orchestrating this attenuation phenotype. Strikingly, the substitution of the nsp2 from the vaccine strain into a highly pathogenic PRRSV (HP-PRRSV) significantly attenuated virulence in piglets while maintaining immunogenicity. The c

SUBMITTER: Bai Y-Z 

PROVIDER: S-EPMC12456151 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature