{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China",
    "Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hao Song"
    },
    {
      "affs": [
        0
      ],
      "name": "Guoqing Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yongbo Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Meng Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Haojie Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zeqing Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinyi Huang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tongqing An",
      "orcid": "0000-0003-4619-4587"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/06jqdzxzkqe2c.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.ppat.1014755",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014755",
  "id": "06jqdzxzkqe2c",
  "issns": [
    "1553-7374",
    "1553-7366"
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  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Biochemistry"
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      "heading",
      "Biology and Life Sciences"
    ],
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      "heading",
      "Biology and life sciences"
    ],
    [
      "heading",
      "DNA construction"
    ],
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      "heading",
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    ],
    [
      "heading",
      "Genomics"
    ],
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      "heading",
      "Infectious Diseases"
    ],
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      "heading",
      "Macromolecular structure analysis"
    ],
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      "heading",
      "Medical Conditions"
    ],
    [
      "heading",
      "Medicine and Health Sciences"
    ],
    [
      "heading",
      "Microbial Genomics"
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    ],
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      "heading",
      "Molecular biology"
    ],
    [
      "heading",
      "Molecular biology techniques"
    ],
    [
      "heading",
      "Nucleic acids"
    ],
    [
      "heading",
      "Organisms"
    ],
    [
      "heading",
      "Plasmid Construction"
    ],
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      "Pulmonology"
    ],
    [
      "heading",
      "RNA"
    ],
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      "RNA structure"
    ],
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    [
      "heading",
      "Transfection"
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    [
      "heading",
      "Viral Genomics"
    ],
    [
      "heading",
      "Viral Replication"
    ],
    [
      "heading",
      "Virology"
    ],
    [
      "heading",
      "Viruses"
    ],
    [
      "openalex",
      "1103|Animal Virus Infections Studies"
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      "/Biology and life sciences/Molecular biology/Macromolecular structure analysis/RNA structure"
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    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/DNA construction/Plasmid construction"
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      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Transfection"
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      "/Biology and life sciences/Organisms/Viruses/RNA viruses"
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      "plos",
      "/Medicine and health sciences/Medical conditions/Infectious diseases/Respiratory infections"
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      "plos",
      "/Medicine and health sciences/Medical conditions/Respiratory disorders/Respiratory infections"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pulmonology/Respiratory disorders/Respiratory infections"
    ],
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      "/Research and analysis methods/Molecular biology techniques/DNA construction/Plasmid construction"
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  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014755&type=printable",
  "pmcid": "PMC13734580",
  "pmid": "42950003",
  "published": "2026-10-28",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/06jqdzxzkqe2c.ris",
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:molecular biology",
      "subfield": "molecular-biology"
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    {
      "field": "biology",
      "origin": "plos:genomics",
      "subfield": "genetics-genomics"
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      "field": "biology",
      "origin": "plos:microbiology",
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    {
      "field": "medicine",
      "origin": "heading:Infectious Diseases",
      "subfield": "infectious-disease"
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  "title": "Defective viral genomes of porcine reproductive and respiratory syndrome virus type 2: Generation, characterization and interference effects on viral replication",
  "title_text": "Defective viral genomes of porcine reproductive and respiratory syndrome virus type 2: Generation, characterization and interference effects on viral replication",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:24:01Z",
  "url": "https://research.draconitic.com/paper/06jqdzxzkqe2c",
  "venue": "PLOS Pathogens",
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}