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.