Progression of nipah virus infection in the African green monkey: Role of macrophages and dendritic cells in early virus spread

End-stage Nipah virus (NiV) infection has been well studied; however, little is known about the development of NiV disease. Here, 12 African green monkeys (AGM) were exposed to NiV and examined over 5 days to investigate NiV pathogenesis. DC-SIGN-positive immature dendritic cells in tonsil and alveolar macrophages were identified at 3 days postinfection (DPI) as early targets, implicating a critical role in the spread of NiV to other tissues. By 5 DPI, NiV spread to endothelium and respiratory epithelium, while fibrin was noted in blood vessels and alveolar spaces. NiV antigen was not detected in cells of CNS tissues from any AGM 3–5 DPI, indicating that neuroinvasion is a late event. NiV elicited a biphasic host response characterized by early consumption of coagulation factors followed by induction of interferon-stimulated cytokines/chemokines and endothelial activation markers. RNA-seq identified a robust, complement-associated immune response in tonsil, versus a muted, interferon-associated response in lung.