Rotavirus viremia and extraintestinal viral infection in the neonatal rat model
Rotavirus viremia and extraintestinal viral infection in the neonatal rat model
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DOI：
10.1128/jvi.80.10.4820-4832.2006
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发表时间：
2006-05-01
影响因子：
5.4
通讯作者：
Estes, Mary K.
中科院分区：
文献类型：
--
作者：
Crawford, Sue E.;Patel, Dinesh G.;Estes, Mary K.
轮状病毒感染小肠的成熟、分化的肠上皮细胞，并通过未知的机制逃逸胃肠道并引起病毒血症。采用新生大鼠轮状病毒感染模型，测定轮状病毒在肠外器官中的病毒血症、传播和病理学动力学。用动物（RRV）或人（HALI 166）轮状病毒或磷酸盐缓冲盐水灌胃接种5日龄大鼠幼仔。从大鼠幼仔的子集收集血液，并且在灌注以去除残余血液后，取出器官并均质化以通过酶联免疫吸附测定分析轮状病毒特异性抗原，并通过荧光焦点测定分析感染性轮状病毒，或固定在福尔马林中用于组织学和免疫组织化学。在轮状病毒感染RRV和HAL 1166后检测到病毒血症。RRV 50%抗原血症剂量为1.8 × 10（3）PFU，50%腹泻剂量为7.7 × 10（5）PFU，表明感染和病毒血症发生在没有腹泻的情况下，检测血液中的轮状病毒抗原是比腹泻更敏感的感染指标。在多个器官（胃、肠、肝、肺、脾、肾、胰腺、胸腺）中检测到轮状病毒抗原和感染性病毒。和膀胱）。轮状病毒感染引起的组织学变化包括门脉和胆管的急性炎症、肝实质和肺实质的微小脂肪变性、坏死和炎性细胞浸润。结构和非结构蛋白与组织病理学在肝脏和肺共定位表明，观察到的组织学变化是由于轮状病毒感染和复制。在肺和血管中的巨噬细胞中也检测到复制轮状病毒，表明轮状病毒传播的可能机制。在被动或主动获得轮状病毒特异性抗体的情况下，观察到肠外感染性轮状病毒，但未观察到腹泻。这些发现改变了以前接受的轮状病毒发病机制的概念，不仅包括胃肠炎，而且还包括病毒血症，它们表明轮状病毒可以在许多不同的器官中引起广泛的全身性疾病。
Rotaviruses infect mature, differentiated enterocytes of the small intestine and, by an unknown mechanism, escape the gastrointestinal tract and cause viremia. The neonatal rat model of rotavirus infection was used to determine the kinetics of viremia, spread, and pathology of rotavirus in extraintestinal organs. Five-day-old rat pups were inoculated intragastrically with an animal (RRV) or human (HALI 166) rotavirus or phosphate-buffered saline. Blood was collected from a subset of rat pups, and following perfusion to remove residual blood, organs were removed and homogenized to analyze rotavirus-specific antigen by enzyme-linked immunosorbent assay and infectious rotavirus by fluorescent focus assay or fixed in formalin for histology and immunohistochemistry. Viremia was detected following rotavirus infection with RRV and HAL1166. The RRV 50% antigenemia dose was 1.8 x 10(3) PFU, and the 50% diarrhea dose was 7.7 x 10(5) PFU, indicating that infection and viremia occurred in the absence of diarrhea and that detecting rotavirus antigen in the blood was a more sensitive measure of infection than diarrhea. Rotavirus antigens and infectious virus were detected in multiple organs (stomach, intestines, liver, lungs, spleen, kidneys, pancreas, thymus. and bladder). Histopathological changes due to rotavirus infection included acute inflammation of the portal tract and bile duct, microsteatosis, necrosis, and inflammatory cell infiltrates in the parenchymas of the liver and lungs. Colocalization of structural and nonstructural proteins with histopathology in the liver and lungs indicated that the histological changes observed were due to rotavirus infection and replication. Replicating rotavirus was also detected in macrophages in the lungs and blood vessels, indicating a possible mechanism of rotavirus dissemination. Extraintestinal infectious rotavirus, but not diarrhea, was observed in the presence of passively or actively acquired rotavirus-specific antibody. These findings alter the previously accepted concept of rotavirus pathogenesis to include not only gastroenteritis but also viremia, and they indicate that rotavirus could cause a broad array of systemic diseases in a number of different organs.