Rotavirus and Serotonin Cross-Talk in Diarrhoea

Rotavirus (RV) has been shown to infect and stimulate secretion of serotonin from human enterochromaffin (EC) cells and to infect EC cells in the small intestine of mice. It remains to identify which intracellularly expressed viral protein(s) is responsible for this novel property and to further establish the clinical role of serotonin in RV infection. First, we found that siRNA specifically silencing NSP4 (siRNANSP4) significantly attenuated secretion of serotonin from Rhesus rotavirus (RRV) infected EC tumor cells compared to siRNAVP4, siRNAVP6 and siRNAVP7. Second, intracellular calcium mobilization and diarrhoeal capacity from virulent and avirulent porcine viruses correlated with the capacity to release serotonin from EC tumor cells. Third, following administration of serotonin, all (10/10) infants, but no (0/8) adult mice, responded with diarrhoea. Finally, blocking of serotonin receptors using Ondansetron significantly attenuated murine RV (strain EDIM) diarrhoea in infant mice (2.9 vs 4.5 days). Ondansetron-treated mice (n = 11) had significantly (p已有研究表明，轮状病毒（Rotavirus, RV）可感染人肠嗜铬细胞（enterochromaffin, EC）并刺激其分泌5-羟色胺（serotonin），同时还可感染小鼠小肠内的肠嗜铬细胞。目前仍有待明确究竟是哪种胞内表达的病毒蛋白介导了这一全新特性，并进一步阐明5-羟色胺在轮状病毒感染过程中的临床作用。其一，相较于siRNAVP4、siRNAVP6及siRNAVP7，特异性沉默非结构蛋白4（NSP4）的小干扰RNA（siRNANSP4）可显著减弱恒河猴轮状病毒（Rhesus rotavirus, RRV）感染的肠嗜铬细胞瘤细胞的5-羟色胺分泌水平。其二，强毒力与弱毒力猪病毒所引发的细胞内钙动员水平及致泻能力，与其从肠嗜铬细胞瘤细胞中释放5-羟色胺的能力相关。其三，给予5-羟色胺后，所有受试婴儿（10/10）均出现腹泻反应，而成年小鼠则无一人出现腹泻反应（0/8）。最后，使用昂丹司琼（Ondansetron）阻断5-羟色胺受体可显著减轻乳鼠感染鼠轮状病毒（毒株EDIM）后的腹泻症状（腹泻持续时间：2.9天 vs 4.5天）。经昂丹司琼处理的小鼠（n=11）的腹泻症状显著改善（p