Changes in small intestinal homeostasis, morphology, and gene expression during rotavirus infection of infant mice
Changes in small intestinal homeostasis, morphology, and gene expression during rotavirus infection of infant mice
复制标题
DOI：
10.1128/jvi.77.24.13005-13016.2003
复制
发表时间：
2003-12-01
影响因子：
5.4
通讯作者：
Einerhand, AWC
中科院分区：
文献类型：
--
作者：
Boshuizen, JA;Reimerink, JHJ;Einerhand, AWC
轮状病毒是婴儿胃肠炎的最重要原因。由于到目前为止还没有对轮状病毒感染的活体粘膜反应进行广泛的研究，我们将小鼠小肠中的病毒复制与粘膜结构、上皮细胞动态平衡、细胞动力学和分化的变化联系起来。给7日龄哺乳BALB/c小鼠接种2×10(4)个小鼠轮状病毒形成单位，并与模拟感染对照组进行比较。记录腹泻疾病和病毒脱落，并评估小肠组织中轮状病毒(NSP4和结构蛋白)和肠道细胞特异性(乳糖酶、SGLT1和L-FABP)基因和蛋白的表达。用免疫组织化学方法检测细胞形态、细胞凋亡、增殖和迁移情况。感染后1~5天出现腹泻，1~10天出现病毒脱落。轮状病毒复制在感染后1天和4天出现两次高峰。组织学改变以空泡化的肠细胞聚集为特征。引人注目的是，空泡细胞的数量超过了可检测到病毒复制的细胞数量。术后1~7d，细胞凋亡和增殖增加，绒毛萎缩。上皮细胞周转率显著高于(
Rotavirus is the most important cause of infantile gastroenteritis. Since in vivo mucosal responses to a rotavirus infection thus far have not been extensively studied, we related viral replication in the murine small intestine to alterations in mucosal structure, epithelial cell homeostasis, cellular kinetics, and differentiation. Seven-day-old suckling BALB/c mice were inoculated with 2 x 10(4) focus-forming units of murine rotavirus and were compared to mock-infected controls. Diarrheal illness and viral shedding were recorded, and small intestinal tissue was evaluated for rotavirus (NSP4 and structural proteins)- and enterocyte- specific (lactase, SGLT1, and L-FABP) mRNA and protein expression. Morphology, apoptosis, proliferation, and migration were evaluated (immuno)histochemically. Diarrhea was observed from days 1 to 5 postinfection, and viral shedding was observed from days 1 to 10. Two peaks of rotavirus replication were observed at 1 and 4 days postinfection. Histological changes were characterized by the accumulation of vacuolated enterocytes. Strikingly, the number of vacuolated cells exceeded the number of cells in which viral replication was detectable. Apoptosis and proliferation were increased from days 1 to 7, resulting in villous atrophy. Epithelial cell turnover was significantly higher (