The Tasmanian Atlantic salmon (Salmo salar) aquaculture industry had remained relatively free of major viral diseases until the recent emergence of pilchard orthomyxovirus (POMV). The virus originally isolated from wild pilchards in Southern Australia is of great concern to the industry as it can cause high mortality. Despite its classification in the Orthomyxoviridae family, POMV is genetically divergent from infectious salmon anaemia virus (ISAV) and potentially represents a new genus within the family. Previous research has produced a formal case definition for clinical POMV, but the molecular events that underpin viral infection have not been characterized. Here we have undertaken a comparative transcriptome analysis of the response of Atlantic salmon kidney cells (ASK) in vitro to both POMV and ISAV using RNA sequencing, by harvesting cells at 6 and 24 h post infection (hpi). Despite their genomic differences, both orthomyxoviruses induced significant, and in some cases similar, innate antiviral responses. Early up-regulation of pathogen recognition receptor genes, RIG-I and TLR3, was observed in response to both viruses and triggered downstream interferon (IFN) responses. Interferon transcripts (IFN-alpha1 and INF-alpha2) were only induced in POMV infected cells at 24 hpi, but IFN-alpha3 was up-regulated in all time points and with both viruses. In addition, a strong induction of antiviral response genes (Mx and ISG15) was observed during the early infection with both viruses. Analysis of transcription factor binding sites in the up-regulated gene sets indicated that the host response to both viruses was largely driven by interferon regulatory factors (IRF) 1 and 2. Only three genes (slc35f2, odf2, LOC106608698) were differentially expressed in opposite directions, up-regulated with POMV and strongly down-regulated with ISAV at 24 hpi. Differential expression of these transcripts is possibly a consequence of virus divergence, but could also be associated to higher viral loads observed in the infection with POMV. Results from this study improve our understanding of the innate immune responses and host-pathogen interactions between POMV and Atlantic salmon. Early host response genes could potentially be exploited as subclinical biomarkers specific to POMV, and improved the development of tools for disease surveillance.

塔斯马尼亚大西洋鲑鱼（Salmo salar）的水产养殖业一直没有出现重大病毒性疾病，直到最近出现沙丁鱼正粘病毒（POMV）。该病毒最初是从南澳大利亚的野生沙丁鱼中分离出来的，因此可能引起高死亡率，因此引起了业界的极大关注。尽管在正粘病毒科中分类，但POMV在遗传上与传染性鲑鱼贫血病毒（ISAV）不同，并且可能代表该科的一个新属。先前的研究已经为临床POMV制定了正式的病例定义，但尚未确定支持病毒感染的分子事件。在这里，我们进行了大西洋鲑鱼肾细胞（ASK）体外反应的比较转录组分析通过感染后（hpi）的6和24小时收获细胞，使用RNA测序将其同时感染POMV和ISAV。尽管它们在基因组上存在差异，但两种正粘病毒都诱导了显着的，在某些情况下相似的先天抗病毒反应。观察到对两种病毒都有反应并触发了下游干扰素（IFN）反应，病原体识别受体基因RIG-1和TLR3的早期上调。干扰素转录本（IFN-alpha1和INF-alpha2）仅在感染后24 h的POMV感染细胞中被诱导，但是IFN-alpha3在所有时间点和两种病毒中均被上调。此外，抗病毒反应基因（Mx和ISG15在两种病毒的早期感染过程中都观察到）。对上调基因集中转录因子结合位点的分析表明，宿主对两种病毒的反应在很大程度上受干扰素调节因子（IRF）1和2的驱动。只有三个基因（slc35f2，odf2和LOC106608698））在相反的方向差异表达，在24 hpi时被POMV上调，而在ISAV中被强烈下调。这些转录本的差异表达可能是病毒发散的结果，但也可能与在POMV感染中观察到的更高的病毒载量有关。这项研究的结果提高了我们对POMV和大西洋鲑鱼之间固有免疫反应和宿主-病原体相互作用的了解。早期宿主反应基因可能被用作POMV的亚临床生物标志物，并改善了疾病监测工具的开发。