Goldin Kerry, Liu Yanling, Rosenke Rebecca, Prado-Smith Jessica, Flagg Meaghan, de Wit Emmie
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Integrated Data Sciences Section, Research Technologies Branch, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.
J Infect Dis. 2025 Feb 4;231(1):219-229. doi: 10.1093/infdis/jiae300.
Nipah virus is an emerging zoonotic virus that causes severe respiratory disease and meningoencephalitis. The pathophysiology of Nipah virus meningoencephalitis is poorly understood.
We have collected the brains of African green monkeys during multiple Nipah virus, Bangladesh studies, resulting in 14 brains with Nipah virus-associated lesions.
The lesions seen in the brain of African green monkeys infected with Nipah virus, Bangladesh were very similar to those observed in humans with Nipah virus, Malaysia infection. We observed viral RNA and antigen within neurons and endothelial cells, within encephalitis foci and in uninflamed portions of the central nervous system (CNS). CD8+ T cells had a consistently high prevalence in CNS lesions. We developed a UNet model for quantifying and visualizing inflammation in the brain in a high-throughput and unbiased manner. While CD8+ T cells had a consistently high prevalence in CNS lesions, the model revealed that CD68+ cells were numerically the immune cell with the highest prevalence in the CNS of Nipah virus-infected animals.
Our study provides an in-depth analysis on Nipah virus infection in the brains of primates, and similarities between lesions in patients and the animals in our study validate this model.
尼帕病毒是一种新出现的人畜共患病毒,可引起严重的呼吸道疾病和脑膜脑炎。人们对尼帕病毒脑膜脑炎的病理生理学了解甚少。
在孟加拉国开展的多项尼帕病毒研究中,我们收集了非洲绿猴的大脑,共获得14个有尼帕病毒相关病变的大脑。
在感染孟加拉国尼帕病毒的非洲绿猴大脑中观察到的病变,与在感染马来西亚尼帕病毒的人类中观察到的病变非常相似。我们在神经元和内皮细胞内、脑炎病灶内以及中枢神经系统(CNS)未发炎部分观察到病毒RNA和抗原。CD8 + T细胞在CNS病变中一直具有较高的患病率。我们开发了一种UNet模型,用于以高通量和无偏倚的方式量化和可视化大脑中的炎症。虽然CD8 + T细胞在CNS病变中一直具有较高的患病率,但该模型显示,在感染尼帕病毒的动物的CNS中,CD68 +细胞在数量上是患病率最高的免疫细胞。
我们的研究对灵长类动物大脑中的尼帕病毒感染进行了深入分析,患者与我们研究中的动物病变之间的相似性验证了该模型。