近日，来自杜克-新加坡国立大学医学院的Eng Eong Ooi和Jenny Guek-Hong Low等研究团队合作发现，代谢紊乱和细胞应激强化了对症状性黄热病感染的易感性。这一研究成果于2019年8月发表在国际学术期刊《自然—医学》上。

为了解症状性感染的分子基础，研究人员在接种活黄热病病毒疫苗（YF17D）之前和之后检查了个体的血液转录组和代谢组。结果发现，具有适应性内质网（ER）应激和基础三羧酸循环活性降低的个体表现出对症状性结果的易感性增加。这些个体中的YF17D感染诱导适应不良的ER应激，从而引发与症状性结果相关的下游促炎反应。因此，这项研究的结果表明，ER应激反应和免疫代谢促进了有症状的黄热病甚至其他黄病毒感染。调节ER应激或代谢可用于预防症状性黄病毒感染结果。

研究人员表示，黄病毒感染导致从无症状到严重疾病的广泛临床结果。虽然已经研究了其与严重疾病的相关性，但是区分有症状与无症状感染的病理生理基础仍然不清楚。

附：英文原文

Title: Metabolic perturbations and cellular stress underpin susceptibility to symptomatic live-attenuated yellow fever infection

Author: Kuan Rong Chan, Esther Shuyi Gan, Candice Yuen Yue Chan, Cui Liang, John Zhong Heng Low, Summer Li-Xin Zhang, Eugenia Ziying Ong, Ashwin Bhatta, Limin Wijaya, Yie Hou Lee, Jenny Guek-Hong Low, Eng Eong Ooi

Issue&Volume: Volume 25 Issue 8, August 2019

Abstract: Flaviviral infections result in a wide spectrum of clinical outcomes, ranging from asymptomatic infection to severe disease. Although the correlates of severe disease have been explored14, the pathophysiology that differentiates symptomatic from asymptomatic infection remains undefined. To understand the molecular underpinnings of symptomatic infection, the blood transcriptomic and metabolomic profiles of individuals were examined before and after inoculation with the live yellow fever viral vaccine (YF17D). It was found that individuals with adaptive endoplasmic reticulum (ER) stress and reduced tricarboxylic acid cycle activity at baseline showed increased susceptibility to symptomatic outcome. YF17D infection in these individuals induced maladaptive ER stress, triggering downstream proinflammatory responses that correlated with symptomatic outcome. The findings of the present study thus suggest that the ER stress response and immunometabolism underpin symptomatic yellow fever and possibly even other flaviviral infections. Modulating either ER stress or metabolism could be exploited for prophylaxis against symptomatic flaviviral infection outcome.

DOI: 10.1038/s41591-019-0510-7

Source:https://www.nature.com/articles/s41591-019-0510-7