Transcriptomic Profiling of Virus-Host Cell Interactions following Chicken Anaemia Virus (CAV) Infection in an In Vivo Model.
Transcriptomic Profiling of Virus-Host Cell Interactions following Chicken Anaemia Virus (CAV) Infection in an In Vivo Model.
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体内模型中鸡肉贫血病毒（CAV）感染后病毒宿主宿主相互作用的转录组分析。
DOI：
10.1371/journal.pone.0134866
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kaiser P
中科院分区：
文献类型：
--
作者：
Giotis ES;Rothwell L;Scott A;Hu T;Talbot R;Todd D;Burt DW;Glass EJ;Kaiser P
鸡贫血病毒（CAV）是一种经济上重要的病毒，其靶向淋巴和成红细胞样祖细胞，导致免疫抑制。本研究旨在研究病毒感染和宿主免疫反应之间的相互作用，以更好地了解导致CAV诱导的免疫抑制的途径。为了模拟CAV在不存在母源性抗体的情况下的垂直传播，感染日龄雏鸡，并通过qRT-PCR和基因表达微阵列在感染后的各个时间点测量它们的应答。通过qRT-PCR确定先天性和适应性免疫应答的特征细胞因子的mRNA表达水平的动力学。还使用鸡免疫相关的5 K微阵列比较了模拟感染（对照）和CAV感染的鸡在14 dpi的整体基因表达谱。虽然在胸腺中，有证据表明CAV感染后诱导了先天性免疫应答，但其幅度有限。几乎没有证据表明任何淋巴组织中存在Th 1适应性免疫应答，而这通常是对病毒感染的反应。除IL-2、IL-13、IL-10和IFNγ在胸腺和骨髓中表达上调外，其他与Th 1、Th 2或Treg亚群相关的细胞因子表达均下调。从微阵列研究中，CAV感染后胸腺和骨髓中表现出显著（大于1.5倍，假发现率<0.05）表达变化的基因主要与T细胞受体信号传导、免疫应答、转录调节、细胞内信号传导和细胞凋亡调节相关。一些衔接蛋白，如src样衔接蛋白（SLA），T细胞受体信号传导的负调节因子和转录因子特殊AT丰富的结合蛋白1（SATB 1）的表达水平显着下调CAV感染，表明这些基因作为病毒感染或细胞防御的调节因子的潜在作用。这些结果扩展了我们对CAV诱导的免疫抑制的理解，并表明CAV感染后存在全局免疫失调。
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.