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Dissecting clinical outcome of porcine circovirus type 2 with in vivo derived transcriptomic signatures of host tissue responses
- Source :
- BMC Genomics, BMC Genomics, Vol 19, Iss 1, Pp 1-15 (2018), BMC GENOMICS
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
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. Electronic supplementary material The online version of this article (10.1186/s12864-018-5217-5) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Swine
animal diseases
Pathogenesis
SUSCEPTIBILITY
Virus Replication
Proteomics
ACTIVATION
STAT3
0403 veterinary science
PMWS
Databases, Genetic
PIGS
Lymphocytes
Cells, Cultured
GENE-EXPRESSION
Host factor
Swine Diseases
Lymphoblast
virus diseases
04 agricultural and veterinary sciences
PCV2
Porcine circovirus
INFECTIONS
Host-Pathogen Interactions
PorSignDB
Systems biology
Functional genomics
RESPIRATORY SYNDROME VIRUS
ORF3 PROTEIN
Research Article
Biotechnology
Circovirus
lcsh:QH426-470
040301 veterinary sciences
lcsh:Biotechnology
Genomics
KAPPA-B
Computational biology
Biology
03 medical and health sciences
lcsh:TP248.13-248.65
Genetics
Animals
Veterinary Sciences
Circoviridae Infections
Transcriptomics
Internet
IL-2
Gene Expression Profiling
Biology and Life Sciences
biology.organism_classification
lcsh:Genetics
030104 developmental biology
REPLICATION
Interleukin-2
Lymph Nodes
Transcriptome
Ex vivo
Subjects
Details
- ISSN :
- 14712164
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- BMC Genomics
- Accession number :
- edsair.doi.dedup.....e24aac9ee2a6d17bd8bdce45befc288d
- Full Text :
- https://doi.org/10.1186/s12864-018-5217-5