Defective Viral Genomes of PRRSV-2 Show Antiviral Activity Against Multiple Strains

Defective viral genomes (DVGs) generated during infection with porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2) have been systematically characterized for the first time, according to a study published in PLOS Pathogens. PRRSV-2 is a major swine pathogen that causes substantial economic losses worldwide, and DVGs are known to regulate viral replication, persistence, and evolution in many RNA viruses, but their characteristics and functions during PRRSV-2 infection had remained unknown.

The research team, led by Hao Song and Tongqing An, analyzed publicly available high-throughput sequencing datasets and characterized DVGs generated during both in vitro and in vivo PRRSV-2 infection. DVG formation was associated with microhomology sequences, RNA secondary structure, and AU-rich sequences, suggesting mechanistic features that favor deletion events during replication.

Mapping of the deletion breakpoints revealed a striking pattern across the viral genome. Break positions were enriched in the GP5/M genomic region, whereas rejoin positions clustered predominantly within the nsp1/nsp2 genomic region. Deletion events within the same gene were highly concentrated in the nsp2 region, where multiple naturally occurring nsp2 deletion sites overlapped with DVG junction sites. The authors suggest that DVG-associated recombination may contribute to the formation of PRRSV-2 nsp2 deletion variants, providing a potential evolutionary link between DVGs and these naturally observed variants.

Functionally, the PRRSV-2-derived DVGs exhibited potent broad-spectrum antiviral activity against multiple prevalent PRRSV-2 lineage strains as well as against PRRSV-1, the related type 1 virus. The study’s authors state that these findings highlight the antiviral potential of PRRSV-2 DVGs. As a systematic characterization based on sequencing datasets and laboratory analysis, the work identifies DVGs as both possible drivers of viral genome diversity and candidate tools for interference with PRRSV replication, while the reported antiviral effects reflect the experimental observations described in the study.

Subject of Research: Characterization of defective viral genomes generated during PRRSV-2 infection and their effects on viral replication.

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

Article References: Song, H., Liu, G., Yang, Y., Chen, M., Wang, H., Liu, Z., Huang, X., & An, T. (2026). Defective viral genomes of porcine reproductive and respiratory syndrome virus type 2: Generation, characterization and interference effects on viral replication. PLOS Pathogens, 22(10), e1014755. https://doi.org/10.1371/journal.ppat.1014755

Image Credits: AI Generated

DOI: 10.1371/journal.ppat.1014755

Keywords: PRRSV-2, defective viral genomes, swine, porcine alveolar macrophages, nsp2 deletion variants, antiviral activity, RNA viruses, viral recombination, microhomology, PLOS Pathogens, Defective, viral