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

The common marmoset ( Callithrix jacchus ) has, in recent years, received more recognition as an ideal non-human primate (NHP) model not only for studies related to neuroscience, but also 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. Four marmosets were infected via the intranasal and intratracheal route and monitored for disease development. We obtained histopathological data, quantified genome copies on >25 tissue-types, and performed RNA-seq on six different organs from all infected and control marmosets. All four subjects developed fatal disease between days 8 and 11 post infection, with three animals developing pulmonary edema and hemorrhage as well as multi-focal hemorrhagic lymphadenopathy. One subject recapitulated neurologic clinical symptoms and cardiomyopathy on gross pathology. In all animals, syncytia were evident in endothelial cells in pulmonary vessels, cells in alveolar septum, and in splenic follicles or red pulp. To define the organ-specific innate and inflammatory responses, we performed RNA-seq on six different organs from all infected and compared to naïve non-infected marmoset tissues. RNA-seq gave 17.4 million reads per sample on average, with the most highly infected tissue sample, the lung of one marmoset, containing >180,000 virus-specific reads. NiV V and W transcripts comprised ∼40% of all phosphoprotein-derived transcripts with V and W being very close to each other proportionally. Principal component analysis showed that in brain stem, the marmoset exhibiting neurological symptoms displayed a unique RNA transcriptome relative even to other infected marmosets. Upregulated genes in the various tissues belonged to distinct GO pathways. Additionally, one male and female animal had detectable viral reads in their ovaries (27,120) and testes (858). 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. ### Competing Interest Statement The authors have declared no competing interest.