Precechtelova Jana, Borsanyiova Maria, Stipalova Darina, Sarmirova Sona, Gomolcak Pavol, Berakova Katarina, Bopegamage Shubhada
Enterovirus Laboratory, Faculty of Medicine, Slovak Medical University, Limbova 12, 83303, Bratislava, Slovak Republic.
Arch Virol. 2015 Jan;160(1):103-15. doi: 10.1007/s00705-014-2236-7. Epub 2014 Oct 8.
Coxsackievirus B4 strain E2 (CVB4-E2) and its association with type 1 diabetes (T1D) have been studied in experimental in vitro and in vivo murine models. CVB4-E2, known to be pancreotropic and diabetogenic in nature, is associated with acute pancreatitis in mice but shows differences in the induction of glycemia after intraperitoneal (i.p.) infection. Therefore, the aim of this work was to study the outcome of oral infection with CVB4-E2 in five mouse strains with different genetic backgrounds: two outbred (Swiss albino, CD1), two inbred (SJL, NOD) and one transgenic (NOD.SCID). Survival rates, fasting blood glucose, histopathology, viral titres and persistence were studied in selected organs and stool samples. Viral protein (VP1), proinflammatory cytokines, and interferon alpha (IFN-α) were analyzed by immunohistochemistry. We observed mortality only in infected NOD and NOD.SCID mice, with differing survival rates implying initial innate protection in the NOD.SCID mice and low virus clearance with replicating virus titres in the studied organs and stool up to day 40 post infection (p.i.). Independent of the mouse strain hyperglycemia, proinflammatory cytokines and histopathological changes were absent in the endocrine pancreas of infected mice. Only the pancreata of the dead NOD.SCID mice showed inflammation even in presence of IFN-α. Host-dependent viral RNA persistence was observed in all outbred mice. In conclusion, oral infection with CVB4-E2, despite the known affinity of this strain towards the pancreatic tissue and the presence of replicating virus, conferred total protection to the endocrine pancreas in all mice and failed to induce the proinflammatory cytokines studied by us.
柯萨奇病毒B4毒株E2（CVB4 - E2）及其与1型糖尿病（T1D）的关联已在体外实验和体内小鼠模型中进行了研究。CVB4 - E2本质上具有嗜胰腺性和致糖尿病性，与小鼠急性胰腺炎有关，但在腹腔内（i.p.）感染后血糖诱导方面存在差异。因此，本研究的目的是研究CVB4 - E2经口感染五种具有不同遗传背景的小鼠品系的结果：两种远交系（瑞士白化小鼠、CD1）、两种近交系（SJL、NOD）和一种转基因系（NOD.SCID）。研究了选定器官和粪便样本中的存活率、空腹血糖、组织病理学、病毒滴度和病毒持续性。通过免疫组织化学分析病毒蛋白（VP1）、促炎细胞因子和干扰素α（IFN -α）。我们仅在感染的NOD和NOD.SCID小鼠中观察到死亡，不同的存活率表明NOD.SCID小鼠最初具有先天保护，并且在感染后40天（p.i.）内，所研究器官和粪便中的病毒复制滴度较低，病毒清除率也较低。无论小鼠品系如何，感染小鼠的内分泌胰腺均未出现高血糖、促炎细胞因子和组织病理学变化。即使存在IFN -α，仅死亡的NOD.SCID小鼠的胰腺显示出炎症。在所有远交系小鼠中均观察到宿主依赖性病毒RNA持续性。总之，尽管已知该毒株对胰腺组织有亲和力且存在病毒复制，但CVB4 - E2经口感染对所有小鼠的内分泌胰腺均提供了完全保护，并且未能诱导我们所研究的促炎细胞因子。
