Defective viral genomes of porcine reproductive and respiratory syndrome virus type 2: Generation, characterization and interference effects on viral replication
- 1State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
- 2Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
Abstract
Porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2) is a major swine pathogen that causes substantial economic losses worldwide. Defective viral genomes (DVGs) are important regulators of viral replication, persistence, and evolution in many RNA viruses. However, the characteristics and functions of DVGs generated during PRRSV-2 infection remain unknown. Here, we systematically analyzed publicly available high-throughput sequencing datasets and characterized DVGs generated during both in vitro and in vivo PRRSV-2 infection. We found that PRRSV-2 preferentially generates large deletion DVGs, particularly in porcine alveolar macrophages (PAMs), and that DVG formation is associated with microhomology sequences, RNA secondary structure and AU-rich sequences. Break positions were enriched in the GP5/M genomic region, whereas rejoin positions clustered predominantly within the nsp1/nsp2 genomic region of the PRRSV-2 genome. Notably, the deletion events within the same gene were highly enriched in the nsp2 region, where multiple naturally occurring nsp2 deletion sites overlapped with DVG junction sites. These findings suggest that DVG-associated recombination may contribute to the formation of PRRSV-2 nsp2 deletion variants. Functionally, PRRSV-2-derived DVGs exhibited potent broad-spectrum antiviral activity against multiple prevalent PRRSV-2 lineage strains and PRRSV-1. Overall, our findings provide the first systematic characterization of PRRSV-2 DVGs, reveal a potential evolutionary link between DVGs and nsp2 deletion variants, and highlight the antiviral potential of PRRSV-2 DVGs. Author summary: Porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2) remains one of the most economically devastating pathogens affecting the global swine industry, yet the characteristics and biological significance of defective viral genomes (DVGs) generated during infection remain unclear. In this study, we provide the first systematic characterization of PRRSV-2 DVGs generated during both in vitro and in vivo infection. We found that PRRSV-2 preferentially produces large deletion DVGs in its natural target cells, porcine alveolar macrophages, and that DVG formation is strongly associated with microhomology sequences, RNA secondary structure and AU-rich regions. Notably, our analyses suggest a potential link between DVG-associated recombination and the emergence of naturally occurring nsp2 deletion variants in PRRSV-2. In addition, representative PRRSV-2-derived DVGs exhibited broad antiviral activity against multiple PRRSV-2 lineages as well as PRRSV-1 strains. Overall, these findings reveal the characteristics and functions of DVGs generated during PRRSV-2 infection and provide new insights into PRRSV-2 DVG research and the development of novel antiviral drugs against PRRSV-2.
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BibTeX
@article{song2026defective,
title = {{Defective viral genomes of porcine reproductive and respiratory syndrome virus type 2: Generation, characterization and interference effects on viral replication}},
author = {Hao Song and Guoqing Liu and Yongbo Yang and Meng Chen and Haojie Wang and Zeqing Liu and Xinyi Huang and Tongqing An},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014755},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014755},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Defective viral genomes of porcine reproductive and respiratory syndrome virus type 2: Generation, characterization and interference effects on viral replication
AU - Hao Song
AU - Guoqing Liu
AU - Yongbo Yang
AU - Meng Chen
AU - Haojie Wang
AU - Zeqing Liu
AU - Xinyi Huang
AU - Tongqing An
PY - 2026
DA - 2026/10/28
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014755
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014755
AB - Porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2) is a major swine pathogen that causes substantial economic losses worldwide. Defective viral genomes (DVGs) are important regulators of viral replication, persistence, and evolution in many RNA viruses. However, the characteristics and functions of DVGs generated during PRRSV-2 infection remain unknown. Here, we systematically analyzed publicly available high-throughput sequencing datasets and characterized DVGs generated during both in vitro and in vivo PRRSV-2 infection. We found that PRRSV-2 preferentially generates large deletion DVGs, particularly in porcine alveolar macrophages (PAMs), and that DVG formation is associated with microhomology sequences, RNA secondary structure and AU-rich sequences. Break positions were enriched in the GP5/M genomic region, whereas rejoin positions clustered predominantly within the nsp1/nsp2 genomic region of the PRRSV-2 genome. Notably, the deletion events within the same gene were highly enriched in the nsp2 region, where multiple naturally occurring nsp2 deletion sites overlapped with DVG junction sites. These findings suggest that DVG-associated recombination may contribute to the formation of PRRSV-2 nsp2 deletion variants. Functionally, PRRSV-2-derived DVGs exhibited potent broad-spectrum antiviral activity against multiple prevalent PRRSV-2 lineage strains and PRRSV-1. Overall, our findings provide the first systematic characterization of PRRSV-2 DVGs, reveal a potential evolutionary link between DVGs and nsp2 deletion variants, and highlight the antiviral potential of PRRSV-2 DVGs. Author summary: Porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2) remains one of the most economically devastating pathogens affecting the global swine industry, yet the characteristics and biological significance of defective viral genomes (DVGs) generated during infection remain unclear. In this study, we provide the first systematic characterization of PRRSV-2 DVGs generated during both in vitro and in vivo infection. We found that PRRSV-2 preferentially produces large deletion DVGs in its natural target cells, porcine alveolar macrophages, and that DVG formation is strongly associated with microhomology sequences, RNA secondary structure and AU-rich regions. Notably, our analyses suggest a potential link between DVG-associated recombination and the emergence of naturally occurring nsp2 deletion variants in PRRSV-2. In addition, representative PRRSV-2-derived DVGs exhibited broad antiviral activity against multiple PRRSV-2 lineages as well as PRRSV-1 strains. Overall, these findings reveal the characteristics and functions of DVGs generated during PRRSV-2 infection and provide new insights into PRRSV-2 DVG research and the development of novel antiviral drugs against PRRSV-2.
SN - 1553-7374
SN - 1553-7366
ER -