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Dissecting clinical outcome of porcine circovirus type 2 with in vivo derived transcriptomic signatures of host tissue responses

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Abstract
Background: Porcine Circovirus Type 2 (PCV2) is a pathogen that has the ability to cause often devastating disease manifestations in pig populations with major economic implications. How PCV2 establishes subclinical persistence and why certain individuals progress to lethal lymphoid depletion remain to be elucidated. Results: Here we present PorSignDB, a gene signature database describing in vivo porcine tissue physiology that we generated from a large compendium of in vivo transcriptional profiles and that we subsequently leveraged for deciphering the distinct physiological states underlying PCV2-affected lymph nodes. This systems genomics approach indicated that subclinical PCV2 infections suppress a myeloid leukocyte mediated immune response. However, in contrast an inflammatory myeloid cell activation is promoted in PCV2 patients with clinical manifestations. Functional genomics further uncovered STAT3 as a druggable PCV2 host factor candidate. Moreover, IL-2 supplementation of primary lymphocytes enabled ex vivo study of PCV2 replication in its target cell, the lymphoblast. Conclusion: Our systematic dissection of the mechanistic basis of PCV2 reveals that subclinical and clinical PCV2 display two diametrically opposed immunotranscriptomic recalibrations that represent distinct physiological states in vivo, which suggests a paradigm shift in this field. Finally, our PorSignDB signature database is publicly available as a community resource (http://www.vetvirology.ugent.be/PorSignDB/, included in Gene Sets from Community Contributors http://software.broadinstitute.org/gsea/msigdb/contributed_genesets.jsp) and provides systems biologists with a valuable tool for catalyzing studies of human and veterinary disease. Finally, a primary porcine lymphoblast cell culture system paves the way for unraveling the impact of host genetics on PCV2 replication.
Keywords
RESPIRATORY SYNDROME VIRUS, GENE-EXPRESSION, ORF3 PROTEIN, KAPPA-B, REPLICATION, PIGS, PCV2, INFECTIONS, ACTIVATION, SUSCEPTIBILITY, PCV2, PorSignDB, PMWS, STAT3, IL-2, Pathogenesis, Transcriptomics, Systems biology

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Citation

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MLA
Van Renne, Nicolaas et al. “Dissecting Clinical Outcome of Porcine Circovirus Type 2 with in Vivo Derived Transcriptomic Signatures of Host Tissue Responses.” BMC GENOMICS 19 (2018): n. pag. Print.
APA
Van Renne, N., Wei, R., Pochet, N., & Nauwynck, H. (2018). Dissecting clinical outcome of porcine circovirus type 2 with in vivo derived transcriptomic signatures of host tissue responses. BMC GENOMICS, 19.
Chicago author-date
Van Renne, Nicolaas, Ruifang Wei, Nathalie Pochet, and Hans Nauwynck. 2018. “Dissecting Clinical Outcome of Porcine Circovirus Type 2 with in Vivo Derived Transcriptomic Signatures of Host Tissue Responses.” Bmc Genomics 19.
Chicago author-date (all authors)
Van Renne, Nicolaas, Ruifang Wei, Nathalie Pochet, and Hans Nauwynck. 2018. “Dissecting Clinical Outcome of Porcine Circovirus Type 2 with in Vivo Derived Transcriptomic Signatures of Host Tissue Responses.” Bmc Genomics 19.
Vancouver
1.
Van Renne N, Wei R, Pochet N, Nauwynck H. Dissecting clinical outcome of porcine circovirus type 2 with in vivo derived transcriptomic signatures of host tissue responses. BMC GENOMICS. 2018;19.
IEEE
[1]
N. Van Renne, R. Wei, N. Pochet, and H. Nauwynck, “Dissecting clinical outcome of porcine circovirus type 2 with in vivo derived transcriptomic signatures of host tissue responses,” BMC GENOMICS, vol. 19, 2018.
@article{8607924,
  abstract     = {Background: Porcine Circovirus Type 2 (PCV2) is a pathogen that has the ability to cause often devastating disease manifestations in pig populations with major economic implications. How PCV2 establishes subclinical persistence and why certain individuals progress to lethal lymphoid depletion remain to be elucidated.
Results: Here we present PorSignDB, a gene signature database describing in vivo porcine tissue physiology that we generated from a large compendium of in vivo transcriptional profiles and that we subsequently leveraged for deciphering the distinct physiological states underlying PCV2-affected lymph nodes. This systems genomics approach indicated that subclinical PCV2 infections suppress a myeloid leukocyte mediated immune response. However, in contrast an inflammatory myeloid cell activation is promoted in PCV2 patients with clinical manifestations. Functional genomics further uncovered STAT3 as a druggable PCV2 host factor candidate. Moreover, IL-2 supplementation of primary lymphocytes enabled ex vivo study of PCV2 replication in its target cell, the lymphoblast.
Conclusion: Our systematic dissection of the mechanistic basis of PCV2 reveals that subclinical and clinical PCV2 display two diametrically opposed immunotranscriptomic recalibrations that represent distinct physiological states in vivo, which suggests a paradigm shift in this field. Finally, our PorSignDB signature database is publicly available as a community resource (http://www.vetvirology.ugent.be/PorSignDB/, included in Gene Sets from Community Contributors http://software.broadinstitute.org/gsea/msigdb/contributed_genesets.jsp) and provides systems biologists with a valuable tool for catalyzing studies of human and veterinary disease. Finally, a primary porcine lymphoblast cell culture system paves the way for unraveling the impact of host genetics on PCV2 replication.},
  articleno    = {831},
  author       = {Van Renne, Nicolaas and Wei, Ruifang and Pochet, Nathalie and Nauwynck, Hans},
  issn         = {1471-2164},
  journal      = {BMC GENOMICS},
  keywords     = {RESPIRATORY SYNDROME VIRUS,GENE-EXPRESSION,ORF3 PROTEIN,KAPPA-B,REPLICATION,PIGS,PCV2,INFECTIONS,ACTIVATION,SUSCEPTIBILITY,PCV2,PorSignDB,PMWS,STAT3,IL-2,Pathogenesis,Transcriptomics,Systems biology},
  language     = {eng},
  pages        = {15},
  title        = {Dissecting clinical outcome of porcine circovirus type 2 with in vivo derived transcriptomic signatures of host tissue responses},
  url          = {http://dx.doi.org/10.1186/s12864-018-5217-5},
  volume       = {19},
  year         = {2018},
}

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