title: Transcriptomic Profiling of Virus-Host Cell Interactions following Chicken Anaemia Virus (CAV) Infection in an In Vivo Model.
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.
authors.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.
authors.forename: Efstathios S
authors.initials: ES
authors.lastname: Giotis
authors.affiliation: Institute for Animal Health, Compton, United Kingdom.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rothwell
authors.affiliation: Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Alistair
authors.initials: A
authors.lastname: Scott
authors.affiliation: Institute for Animal Health, Compton, United Kingdom.
authors.forename: Tuanjun
authors.initials: T
authors.lastname: Hu
authors.affiliation: The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Talbot
authors.affiliation: Agri-Food and Biosciences Institute, Belfast, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Todd
authors.affiliation: The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: David W
authors.initials: DW
authors.lastname: Burt
authors.affiliation: The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Glass
authors.affiliation: Institute for Animal Health, Compton, United Kingdom.
authors.forename: Pete
authors.initials: P
authors.lastname: Kaiser
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D030161:Avian Proteins / Q000235:genetics; D002460:Cell Line; D017727:Chicken anemia virus / Q000254:growth & development* / Q000502:physiology; D018173:Circoviridae Infections / Q000235:genetics* / Q000821:virology; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D054884:Host-Pathogen Interactions; D007107:Immune System / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011201:Poultry Diseases / Q000235:genetics* / Q000821:virology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
chemical_list: D030161:Avian Proteins; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell