Characterizing differential individual response to porcine reproductive and respiratory syndrome virus infection through statistical and functional analysis of gene expression

Arceo, Maria E.; Ernst, Catherine W.; Lunney, Joan K.; Choi, Igseo; Raney, Nancy E.; Huang, Tinghua; Tuggle, Christopher K.; Rowland, R.; Steibel, Juan P.

doi:10.3389/fgene.2012.00321

Cited by 21 publications

(31 citation statements)

References 61 publications

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“…4–6) significantly involved in response to PRRSV infection in macrophages at different activation statuses. It is noteworthy that our RNA-Seq analysis using polarized macrophages revealed a dozen more significant pathways that have not been reported in previous transcriptomic analyses using PRRSV-infected tissues or cells [27]–[34]. Furthermore, analysis of two key signaling pathways, AMPK-mediated and epigenetic mechanisms, not only clustered the pathway-inclusive DEGs pertaining to each activation status, but also functionally validated the involvement of AMPK-mediated and epigenetic pathways in regulation of antiviral response to PRRSV infection in cells.…”

Section: Discussionmentioning

confidence: 46%

Genome-Wide Analysis of Antiviral Signature Genes in Porcine Macrophages at Different Activation Statuses

et al. 2014

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Macrophages (MФs) can be polarized to various activation statuses, including classical (M1), alternative (M2), and antiviral states. To study the antiviral activation status of porcine MФs during porcine reproductive and respiratory syndrome virus (PRRSV) infection, we used RNA Sequencing (RNA-Seq) for transcriptomic analysis of differentially expressed genes (DEGs). Sequencing assessment and quality evaluation showed that our RNA-Seq data met the criteria for genome-wide transcriptomic analysis. Comparisons of any two activation statuses revealed more than 20,000 DEGs that were normalized to filter out 153–5,303 significant DEGs [false discovery rate (FDR) ≤0.001, fold change ≥2] in each comparison. The highest 5,303 significant DEGs were found between lipopolysaccharide- (LPS) and interferon (IFN)γ-stimulated M1 cells, whereas only 153 significant DEGs were detected between interleukin (IL)-10-polarized M2 cells and control mock-activated cells. To identify signature genes for antiviral regulation pertaining to each activation status, we identified a set of DEGs that showed significant up-regulation in only one activation state. In addition, pathway analyses defined the top 20–50 significantly regulated pathways at each activation status, and we further analyzed DEGs pertinent to pathways mediated by AMP kinase (AMPK) and epigenetic mechanisms. For the first time in porcine macrophages, our transcriptomic analyses not only compared family-wide differential expression of most known immune genes at different activation statuses, but also revealed transcription evidence of multiple gene families. These findings show that using RNA-Seq transcriptomic analyses in virus-infected and status-synchronized macrophages effectively profiled signature genes and gene response pathways for antiviral regulation, which may provide a framework for optimizing antiviral immunity and immune homeostasis.

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Section: Discussionmentioning

confidence: 46%

Genome-Wide Analysis of Antiviral Signature Genes in Porcine Macrophages at Different Activation Statuses

et al. 2014

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“…Differences in animal age were not important, as we obtained similar results with 6 week-old and 1 year-old blood donors. However, the genetic of the pigs could possibly play a role since differential expression genes, especially IFNA, have been highlighted in phenotypic pig groups in response to PRRSV [41]. Another difference compared to the data from Calzada-Nova et al could be the methodology and cell isolation procedures.…”

Section: Discussionmentioning

confidence: 93%

Impact of genotype 1 and 2 of porcine reproductive and respiratory syndrome viruses on interferon-α responses by plasmacytoid dendritic cells

Baumann

Mateu

Murtaugh

et al. 2013

Vet Res

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Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) infections are characterized by prolonged viremia and viral shedding consistent with incomplete immunity. Type I interferons (IFN) are essential for mounting efficient antiviral innate and adaptive immune responses, but in a recent study, North American PRRSV genotype 2 isolates did not induce, or even strongly inhibited, IFN-α in plasmacytoid dendritic cells (pDC), representing “professional IFN-α-producing cells”. Since inhibition of IFN-α expression might initiate PRRSV pathogenesis, we further characterized PRRSV effects and host modifying factors on IFN-α responses of pDC. Surprisingly, a variety of type 1 and type 2 PRRSV directly stimulated IFN-α secretion by pDC. The effect did not require live virus and was mediated through the TLR7 pathway. Furthermore, both IFN-γ and IL-4 significantly enhanced the pDC production of IFN-α in response to PRRSV exposure. PRRSV inhibition of IFN-α responses from enriched pDC stimulated by CpG oligodeoxynucleotides was weak or absent. VR-2332, the prototype genotype 2 PRRSV, only suppressed the responses by 34%, and the highest level of suppression (51%) was induced by a Chinese highly pathogenic PRRSV isolate. Taken together, these findings demonstrate that pDC respond to PRRSV and suggest that suppressive activities on pDC, if any, are moderate and strain-dependent. Thus, pDC may be a source of systemic IFN-α responses reported in PRRSV-infected animals, further contributing to the puzzling immunopathogenesis of PRRS.

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“…Initial work using microarrays showed a number of genes that were differentially expressed between animals with high and low host response to PRRS (Arceo et al, 2013). Using microarray gene expression profiles, Schroyen et al (2015) identified differences in blood RNA patterns in early responses to PRRSV infection between pigs with extreme phenotypes or with a different WUR genotype.…”

Section: Additional Gene Expression and Immune Response Analysesmentioning

confidence: 99%

Host genetics of response to porcine reproductive and respiratory syndrome in nursery pigs

Dekkers

Rowland

Lunney

et al. 2017

Veterinary Microbiology

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A B S T R A C TPRRS is the most costly disease in the US pig industry. While vaccination, biosecurity and eradication effort have had some success, the variability and infectiousness of PRRS virus strains have hampered the effectiveness of these measures. We propose the use of genetic selection of pigs as an additional and complementary effort. Several studies have shown that host response to PRRS infection has a sizeable genetic component and recent advances in genomics provide opportunities to capitalize on these genetic differences and improve our understanding of host response to PRRS. While work is also ongoing to understand the genetic basis of host response to reproductive PRRS, the focus of this review is on research conducted on host response to PRRS in the nursery and grow-finish phase as part of the PRRS Host Genetics Consortium. Using experimental infection of large numbers of commercial nursery pigs, combined with deep phenotyping and genomics, this research has identified a major gene that is associated with host response to PRRS. Further functional genomics work identified the GBP5 gene as harboring the putative causative mutation. GBP5 is associated with innate immune response. Subsequent work has validated the effect of this genomic region on host response to a second PRRSV strain and to PRRS vaccination and co-infection of nursery pigs with PRRSV and PCV2b. A genetic marker near GBP5 is available to the industry for use in selection. Genetic differences in host response beyond GBP5 appear to be highly polygenic, i.e. controlled by many genes across the genome, each with a small effect. Such effects can by capitalized on in a selection program using genomic prediction on large numbers of genetic markers across the genome. Additional work has also identified the genetic basis of antibody response to PRRS, which could lead to the use of vaccine response as an indicator trait to select for host response to PRRS. Other genomic analyses, including gene expression analyses, have identified genes and modules of genes that are associated with differences in host response to PRRS and can be used to further understand and utilize differences in host response. Together, these results demonstrate that genetic selection can be an additional and complementary tool to combat PRRS in the swine industry.

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Characterizing differential individual response to porcine reproductive and respiratory syndrome virus infection through statistical and functional analysis of gene expression

Cited by 21 publications

References 61 publications

Genome-Wide Analysis of Antiviral Signature Genes in Porcine Macrophages at Different Activation Statuses

Genome-Wide Analysis of Antiviral Signature Genes in Porcine Macrophages at Different Activation Statuses

Impact of genotype 1 and 2 of porcine reproductive and respiratory syndrome viruses on interferon-α responses by plasmacytoid dendritic cells

Host genetics of response to porcine reproductive and respiratory syndrome in nursery pigs

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