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Transcriptomic Profiling of Virus-Host Cell Interactions following Chicken Anaemia Virus (CAV) Infection in an In Vivo Model.

Giotis ES, Rothwell L, Scott A, Hu T, Talbot R, Todd D, Burt DW, Glass EJ, Kaiser P - PLoS ONE (2015)

Bottom Line: The kinetics of mRNA expression levels of signature cytokines of innate and adaptive immune responses were determined by qRT-PCR.Most cytokines associated with Th1, Th2 or Treg subsets were down-regulated, except IL-2, IL-13, IL-10 and IFNγ, which were all up-regulated in thymus and bone marrow.From the microarray studies, genes that exhibited significant (greater than 1.5-fold, false discovery rate <0.05) changes in expression in thymus and bone marrow on CAV infection were mainly associated with T-cell receptor signalling, immune response, transcriptional regulation, intracellular signalling and regulation of apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Agri-Food and Biosciences Institute, Belfast, United Kingdom; Queen's University Belfast, Belfast, United Kingdom; The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, United Kingdom.

ABSTRACT
Chicken Anaemia Virus (CAV) is an economically important virus that targets lymphoid and erythroblastoid progenitor cells leading to immunosuppression. This study aimed to investigate the interplay between viral infection and the host's immune response to better understand the pathways that lead to CAV-induced immunosuppression. To mimic vertical transmission of CAV in the absence of maternally-derived antibody, day-old chicks were infected and their responses measured at various time-points post-infection by qRT-PCR and gene expression microarrays. The kinetics of mRNA expression levels of signature cytokines of innate and adaptive immune responses were determined by qRT-PCR. The global gene expression profiles of mock-infected (control) and CAV-infected chickens at 14 dpi were also compared using a chicken immune-related 5K microarray. Although in the thymus there was evidence of induction of an innate immune response following CAV infection, this was limited in magnitude. There was little evidence of a Th1 adaptive immune response in any lymphoid tissue, as would normally be expected in response to viral infection. Most cytokines associated with Th1, Th2 or Treg subsets were down-regulated, except IL-2, IL-13, IL-10 and IFNγ, which were all up-regulated in thymus and bone marrow. From the microarray studies, genes that exhibited significant (greater than 1.5-fold, false discovery rate <0.05) changes in expression in thymus and bone marrow on CAV infection were mainly associated with T-cell receptor signalling, immune response, transcriptional regulation, intracellular signalling and regulation of apoptosis. Expression levels of a number of adaptor proteins, such as src-like adaptor protein (SLA), a negative regulator of T-cell receptor signalling and the transcription factor Special AT-rich Binding Protein 1 (SATB1), were significantly down-regulated by CAV infection, suggesting potential roles for these genes as regulators of viral infection or cell defence. These results extend our understanding of CAV-induced immunosuppression and suggest a global immune dysregulation following CAV infection.

No MeSH data available.


Related in: MedlinePlus

Ingenuity pathway analysis showing the most highly scoring canonical pathways (according to P value) associated with the response of thymocytes to CAV infection.Five pathways had a P value < 0.05. The orange line represents the ratio of the number of differentially expressed thymus genes in a particular pathway whose expression is correlated with cellular response towards CAV divided by the total number of genes that make up that pathway. Blue bars represent the P value for each pathway and are expressed as -1 times the log of the P value. The threshold line corresponds to a P value of 0.05.
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pone.0134866.g001: Ingenuity pathway analysis showing the most highly scoring canonical pathways (according to P value) associated with the response of thymocytes to CAV infection.Five pathways had a P value < 0.05. The orange line represents the ratio of the number of differentially expressed thymus genes in a particular pathway whose expression is correlated with cellular response towards CAV divided by the total number of genes that make up that pathway. Blue bars represent the P value for each pathway and are expressed as -1 times the log of the P value. The threshold line corresponds to a P value of 0.05.

Mentions: IPA software was used to identify the main host functions and canonical pathways, from the microarray data (S2 File), modulated by CAV infection. Differentially-expressed genes in the thymus fell into diverse functional categories, including cell-cell signalling, immune cell trafficking, inflammatory response, cell death, molecular transport, post-translational modification, cellular growth, development and proliferation (S1 File). Of the 34 differentially modulated canonical pathways that were identified (S1 File), the T-cell receptor (TCR) signalling pathway appeared to be most important for the response of the thymus cells to CAV (P value: 1.67E-04, Fig 1).


Transcriptomic Profiling of Virus-Host Cell Interactions following Chicken Anaemia Virus (CAV) Infection in an In Vivo Model.

Giotis ES, Rothwell L, Scott A, Hu T, Talbot R, Todd D, Burt DW, Glass EJ, Kaiser P - PLoS ONE (2015)

Ingenuity pathway analysis showing the most highly scoring canonical pathways (according to P value) associated with the response of thymocytes to CAV infection.Five pathways had a P value < 0.05. The orange line represents the ratio of the number of differentially expressed thymus genes in a particular pathway whose expression is correlated with cellular response towards CAV divided by the total number of genes that make up that pathway. Blue bars represent the P value for each pathway and are expressed as -1 times the log of the P value. The threshold line corresponds to a P value of 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526643&req=5

pone.0134866.g001: Ingenuity pathway analysis showing the most highly scoring canonical pathways (according to P value) associated with the response of thymocytes to CAV infection.Five pathways had a P value < 0.05. The orange line represents the ratio of the number of differentially expressed thymus genes in a particular pathway whose expression is correlated with cellular response towards CAV divided by the total number of genes that make up that pathway. Blue bars represent the P value for each pathway and are expressed as -1 times the log of the P value. The threshold line corresponds to a P value of 0.05.
Mentions: IPA software was used to identify the main host functions and canonical pathways, from the microarray data (S2 File), modulated by CAV infection. Differentially-expressed genes in the thymus fell into diverse functional categories, including cell-cell signalling, immune cell trafficking, inflammatory response, cell death, molecular transport, post-translational modification, cellular growth, development and proliferation (S1 File). Of the 34 differentially modulated canonical pathways that were identified (S1 File), the T-cell receptor (TCR) signalling pathway appeared to be most important for the response of the thymus cells to CAV (P value: 1.67E-04, Fig 1).

Bottom Line: The kinetics of mRNA expression levels of signature cytokines of innate and adaptive immune responses were determined by qRT-PCR.Most cytokines associated with Th1, Th2 or Treg subsets were down-regulated, except IL-2, IL-13, IL-10 and IFNγ, which were all up-regulated in thymus and bone marrow.From the microarray studies, genes that exhibited significant (greater than 1.5-fold, false discovery rate <0.05) changes in expression in thymus and bone marrow on CAV infection were mainly associated with T-cell receptor signalling, immune response, transcriptional regulation, intracellular signalling and regulation of apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Agri-Food and Biosciences Institute, Belfast, United Kingdom; Queen's University Belfast, Belfast, United Kingdom; The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, United Kingdom.

ABSTRACT
Chicken Anaemia Virus (CAV) is an economically important virus that targets lymphoid and erythroblastoid progenitor cells leading to immunosuppression. This study aimed to investigate the interplay between viral infection and the host's immune response to better understand the pathways that lead to CAV-induced immunosuppression. To mimic vertical transmission of CAV in the absence of maternally-derived antibody, day-old chicks were infected and their responses measured at various time-points post-infection by qRT-PCR and gene expression microarrays. The kinetics of mRNA expression levels of signature cytokines of innate and adaptive immune responses were determined by qRT-PCR. The global gene expression profiles of mock-infected (control) and CAV-infected chickens at 14 dpi were also compared using a chicken immune-related 5K microarray. Although in the thymus there was evidence of induction of an innate immune response following CAV infection, this was limited in magnitude. There was little evidence of a Th1 adaptive immune response in any lymphoid tissue, as would normally be expected in response to viral infection. Most cytokines associated with Th1, Th2 or Treg subsets were down-regulated, except IL-2, IL-13, IL-10 and IFNγ, which were all up-regulated in thymus and bone marrow. From the microarray studies, genes that exhibited significant (greater than 1.5-fold, false discovery rate <0.05) changes in expression in thymus and bone marrow on CAV infection were mainly associated with T-cell receptor signalling, immune response, transcriptional regulation, intracellular signalling and regulation of apoptosis. Expression levels of a number of adaptor proteins, such as src-like adaptor protein (SLA), a negative regulator of T-cell receptor signalling and the transcription factor Special AT-rich Binding Protein 1 (SATB1), were significantly down-regulated by CAV infection, suggesting potential roles for these genes as regulators of viral infection or cell defence. These results extend our understanding of CAV-induced immunosuppression and suggest a global immune dysregulation following CAV infection.

No MeSH data available.


Related in: MedlinePlus