Identification of differentially expressed Atlantic salmon miRNAs responding to salmonid alphavirus (SAV) infection.
Identification of differentially expressed Atlantic salmon miRNAs responding to salmonid alphavirus (SAV) infection.
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DOI：
10.1186/s12864-017-3741-3
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发表时间：
2017-05-04
期刊：
影响因子：
4.4
通讯作者：
Høyheim B
中科院分区：
文献类型：
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作者：
Andreassen R;Woldemariam NT;Egeland IØ;Agafonov O;Sindre H;Høyheim B
MicroRNA (miRNA) 通过基因表达的转录后负调节来控制多种生物过程，包括先天免疫反应。由于没有关于 miRNA 在大西洋鲑鱼病毒性疾病中的作用的研究，我们的目的是鉴定对鲑鱼甲病毒 (SAV) 感染有反应的 miRNA。在与不同死亡率相关的 SAV 分离株感染后的不同时间点研究了它们的表达。此外，对已鉴定的 miRNA 的基因组序列进行分析，以揭示推定的顺式调控元件，最后预测其推定的靶基因。鉴定出二十种差异表达的 miRNA（DE miRNA）。其中大多数的表达在感染后增加，并在病毒载量稳定或减少后达到最大水平。另一方面，一些 miRNA（例如 miRNA-21 家族）在感染后的早期时间点表现出表达下降。与不同 SAV 分离株相关的单个 miRNA 的时间表达存在显着差异。 SAV 反应性免疫网络基因中的靶基因预测表明，17 个 DE miRNA 可以靶向 24 个基因（例如 IRF3、IRF7）。应用大西洋鲑鱼转录组作为输入，另外 28 个免疫网络基因被揭示为推定目标（例如 IRF5、IRF4）。大多数预测的靶基因都会促进炎症反应。 miRNA 基因的上游序列揭示了高密度的顺式调控序列，称为免疫网络转录因子 (TF) 的结合位点。因此，晚期的高表达可能是由于免疫反应激活的 TF 促进转录增加所致。基于计算机靶标预测，我们讨论了它们作为炎症早期促进剂或晚期抑制剂的假定作用。我们认为与不同 SAV 分离株相关的表达差异可能导致其死亡率差异。这项研究代表了探索在大西洋鲑鱼病毒与宿主相互作用中重要的 miRNA 的第一步。我们鉴定了几种响应 SAV 感染的 miRNA。有些可能会抑制有害炎症，而另一些可能会促进早期免疫反应。它们的预测功能需要在功能测定中得到验证和进一步研究，以充分了解它们在免疫稳态中的作用。本文的在线版本 (doi:10.1186/s12864-017-3741-3) 包含补充材料，可供授权用户使用。
MicroRNAs (miRNAs) control multiple biological processes including the innate immune responses by negative post-transcriptional regulation of gene expression. As there were no studies on the role(s) of miRNAs in viral diseases in Atlantic salmon, we aimed to identify miRNAs responding to salmonid alphavirus (SAV) infection. Their expression were studied at different time points post infection with SAV isolates associated with different mortalities. Furthermore, the genome sequences of the identified miRNAs were analysed to reveal putative cis-regulatory elements, and, finally, their putative target genes were predicted. Twenty differentially expressed miRNAs (DE miRNAs) were identified. The expression of the majority of these increased post infection with maximum levels reached after the viral load were stabilized or decreasing. On the other hand, some miRNAs (e.g. the miRNA-21 family) showed decreased expression at the early time points post infection. There were significant differences in the temporal expression of individual miRNA associated with different SAV isolates. Target gene prediction in SAV responsive immune network genes showed that seventeen of the DE miRNAs could target 24 genes (e.g. IRF3, IRF7). Applying the Atlantic salmon transcriptome as input 28 more immune network genes were revealed as putative targets (e.g. IRF5, IRF4). The majority of the predicted target genes promote inflammatory response. The upstream sequences of the miRNA genes revealed a high density of cis-regulatory sequences known as binding sites for immune network transcription factors (TFs). A high expression in the late phase could therefore be due to increased transcription promoted by immune response activated TFs. Based on the in silico target predictions, we discuss their putative roles as early promotors or late inhibitors of inflammation. We propose that the differences in expressions associated with different SAV isolates could contribute to their differences in mortality rates. This study represents the first steps in exploring miRNAs important in viral-host interaction in Atlantic salmon. We identified several miRNAs responding to SAV infection. Some likely to prohibit harmful inflammation while other may promote an early immune response. Their predicted functions need to be validated and further studied in functional assays to fully understand their roles in immune homeostasis. The online version of this article (doi:10.1186/s12864-017-3741-3) contains supplementary material, which is available to authorized users.