Nipah virus Bangladesh infection elicits organ-specific innate and inflammatory responses in the marmoset model

Abstract

The common marmoset (Callithrix jacchus) is increasingly recognized as an ideal non-human primate (NHP) at high-biocontainment due to its smaller size and relative ease of handling. Here, we evaluated the susceptibility and pathogenesis of Nipah virus Bangladesh strain (NiVB) infection in marmosets at biosafety level 4. Infection via the intranasal and intratracheal route resulted in fatal disease in all four infected marmosets. Three developed pulmonary edema and hemorrhage as well as multi-focal hemorrhagic lymphadenopathy, while one recapitulated neurologic clinical symptoms and cardiomyopathy on gross pathology. Organ-specific innate and inflammatory responses were characterized by RNA-seq in six different tissues from infected and control marmosets. Notably, a unique transcriptome was revealed in the brainstem of the marmoset exhibiting neurological symptoms. Our results provide a more comprehensive understanding of NiV pathogenesis in an accessible and novel NHP model, closely reflecting clinical disease as observed in NiV patients.