Nipah Virus-Associated Neuropathology in African Green Monkeys During Acute Disease and Convalescence

Abstract

Abstract Background Nipah virus is an emerging zoonotic virus that causes severe respiratory disease and meningoencephalitis. The pathophysiology of Nipah virus meningoencephalitis is poorly understood. Methods We have collected the brains of African green monkeys during multiple Nipah virus, Bangladesh studies, resulting in 14 brains with Nipah virus-associated lesions. Results 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. Conclusions 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.