Tilapia lake virus (TiLV) is regarded as one of the most important pathogens in tilapia aquaculture worldwide. Despite this, little is known regarding disease pathogenesis and immune responses to infection. The main objective of this study was to investigate the tissue distribution, histopathological changes, and immune response of fish exposed to TiLV. Nile tilapia (Oreochromis niloticus) maintained at 25 ± 2 °C were challenged with TiLV via intragastric-gavage. At 0.5, 1, 3, 5, 7, 10 and 15 days post-challenge (dpc), six fish per treatment were euthanized and subjected to complete necropsy. TiLV exposed fish presented 45% cumulative mortality at the end of the study. Gross lesions included cutaneous petechiae and ecchymoses, scale losses, skin ulcers, and exophthalmia. Mild multifocal hepatocellular degeneration and necrosis was observed as early as 3 dpc occasionally accompanied by syncytial formation, intracytoplasmic inclusion bodies, and inflammatory infiltrates of lymphocytes at subsequent time points. Necrosis of epithelial cells of the gastric glands and intestinal glands was also observed as early as 5 dpc. Intestinal samples showed reactive in situ hybridization signals as early as 1 dpc. No other lesions were observed in the brain or other organs. Histological changes were associated with viral dissemination and disease progression, as evidenced by increased TiLV detection in the intestine, gills, liver and spleen. Highest TiLV abundance was detected 7 dpc in gills, intestine, and liver showing an average of 6 LOG genome equivalent per ng of total RNA. Different transcript abundance was detected for the pro-inflammatory cytokine interleukin-1β and interferon-induced myxovirus resistance protein gene in the mucosal sites (gills and intestine). Interferon regulatory transcription factor 3 transcript was more abundant in systemic organs (liver and spleen) while the expression in gills and intestine showed mixed expression at different time points. On the other hand, transforming growth factor β expression patterns differed amongst the tissues with a trend towards downregulation of the gene in liver and gills, and a trend towards upregulation in the spleen and intestine. Overall, these results demonstrate the intestinal routes as a main port of entry for TiLV, which subsequently spreads systematically throughout the fish body.

罗非鱼湖病毒（TiLV）被认为是全球罗非鱼水产养殖中最重要的病原体之一。尽管如此，关于疾病的发病机理和对感染的免疫反应知之甚少。这项研究的主要目的是调查暴露于TiLV的鱼的组织分布，组织病理学变化和免疫反应。尼罗罗非鱼（Oreochromis niloticus）维持在25±2°C的TiLV通过胃内灌胃法攻击。在攻击后0.5、1、3、5、7、10和15天（dpc），对每条处理的6条鱼实施安乐死并进行完整的尸检。在研究结束时，暴露于TiLV的鱼的累积死亡率为45％。肉眼可见的病变包括皮肤瘀斑和瘀斑，水垢消失，皮肤溃疡和眼球突出。早在3 dpc时观察到轻度多灶性肝细胞变性和坏死，偶尔在随后的时间点出现合胞体形成，胞浆内包涵体和淋巴细胞的炎性浸润。早在5 dpc时也观察到胃腺和肠腺上皮细胞坏死。肠道样本显示原位反应杂交信号最早可达到1 dpc。在大脑或其他器官中未观察到其他病变。组织学变化与病毒传播和疾病进展相关，如肠，腮、,、肝和脾中TiLV检测增加所证明的。在腮，肠和肝脏中检测到最高7 dpc的TiLV丰度，显示每ng总RNA平均6 LOG基因组当量。对促炎细胞因子白细胞介素-1，检测不同转录物丰度β和在粘膜部位（g和肠）的干扰素诱导的粘液病毒抵抗蛋白基因。全身器官（肝脏和脾脏）中的干扰素调节转录因子3转录物更为丰富，而g和肠中的表达则在不同时间点混合表达。另一方面，组织中转化生长因子β的表达模式不同，肝和g中的基因表达下调，脾脏和肠的表达上调。总的来说，这些结果表明肠道途径是TiLV的主要进入途径，随后系统地传播到整个鱼体内。