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Role of nitric oxide during rotavirus infection.

机译:一氧化氮在轮状病毒感染中的作用。

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The pathophysiological mechanisms behind rotavirus-induced diarrhoea still remain incomplete. Current views suggest that the non-structural protein 4 (NSP4) of rotavirus and the enteric nervous system (ENS) participate in water secretion and diarrhoea. In the present work the role of nitric oxide (NO) in rotavirus infection and disease has been studied in vitro, mice and humans. Incubation of human intestinal epithelial cells (HT-29) with purified NSP4 but not with infectious virus produced NO2/NO3 accumulation in the incubation media. The NSP4-induced release of NO metabolites occurred within the first minutes after the addition of the toxin. Mice infected with murine rotavirus (strain EDIM) accumulated NO2/NO3 in the urine at the onset for diarrhoea. Following rotavirus infection, inducible nitric oxide synthetase (iNOS) mRNA was upregulated in ileum, but not in duodenum or jejunum of newborn pups within 5 days post-infection. A prospective clinical study including 46 children with acute rotavirus infection and age-matched controls concluded that rotavirus infection stimulates NO production during the course of the disease (P < 0.001). These observations identify NO as an important mediator of host responses during rotavirus infection.
机译:轮状病毒引起的腹泻的病理生理机制仍然不完全。当前的观点表明,轮状病毒的非结构蛋白4(NSP4)和肠神经系统(ENS)参与了水的分泌和腹泻。在本研究中,已经在体外,小鼠和人类中研究了一氧化氮(NO)在轮状病毒感染和疾病中的作用。将人肠上皮细胞(HT-29)与纯化的NSP4孵育,而不与感染性病毒孵育,在培养液中会产生NO2 / NO3积累。 NSP4诱导的NO代谢产物释放在添加毒素后的第一分钟内发生。感染鼠轮状病毒(EDIM株)的小鼠在腹泻开始时在尿液中积累了NO2 / NO3。轮状病毒感染后,在感染后5天内,回肠的诱导型一氧化氮合成酶(iNOS)mRNA上调,但新生幼鼠的十二指肠或空肠未上调。一项包括46例急性轮状病毒感染儿童和年龄相匹配的对照的前瞻性临床研究得出结论,轮状病毒感染可在疾病过程中刺激NO的产生(P <0.001)。这些观察结果确定NO是轮状病毒感染期间宿主反应的重要介质。

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