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

Nicolaas Van Renne,Hans J Nauwynck,Nathalie Pochet,Ruifang Wei

doi:10.1186/s12864-018-5217-5

Abstract

BackgroundPorcine 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.ResultsHere 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.ConclusionOur 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.

Highlights

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
PCV2 is acknowledged as the causative agent of post-weaning multisystemic wasting syndrome (PMWS), PCV2 infection alone generally results in a persistent low-level replication without clinical signs [5]
Gene Ontology (GO) biological process gene enrichment was performed for every gene set, and provides an overview of the biological information captured in this signature database (Additional file 1)

Summary

Introduction

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. Porcine circovirus type 2 (PCV2) is a very small circular single-stranded DNA virus that circulates endemically in swine populations. PCV2 is acknowledged as the causative agent of PMWS, PCV2 infection alone generally results in a persistent low-level replication without clinical signs [5]. PCV2 circulates endemically in pig populations as covert subclinical infections, seemingly undeterred by vaccination [6]. In a real-life setting, piglets are mostly affected after weaning. This presumably happens because maternal antibodies cease to provide protection [9].

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Conclusion