Defective viral genomes of porcine reproductive and respiratory syndrome virus type 2: Generation, characterization and interference effects on viral replication.

PRRSV-2 preferentially generates large deletion defective viral genomes in porcine alveolar macrophages, with breakpoints enriched in GP5/M and rejoin sites clustered in nsp1/nsp2.

• Why it matters: DVGs can regulate viral replication, persistence, and evolution, but PRRSV-2 DVG characteristics and functions during infection were unknown.
• What they did: The study systematically analyzed public high-throughput sequencing datasets from in vitro and in vivo PRRSV-2 infection, linking DVG formation to microhomology, RNA secondary structure, and AU-rich sequences.
• The result: PRRSV-2-derived DVGs showed potent broad-spectrum antiviral activity against multiple prevalent PRRSV-2 lineage strains and PRRSV-1, suggesting DVG-associated recombination may form nsp2 deletion variants.