Progression of Nipah virus infection in African green monkeys: role of macrophages and dendritic cells in early virus spread

ABSTRACT: Nipah virus (NiV) infection causes severe respiratory disease and encephalitis in humans and nonhuman primates with high case fatality rates. While end-stage disease in primates has been well studied, particularly in African green monkeys (AGM), little is known about the development of NiV disease. Here, 12 AGM were infected with NiV and examined sequentially over 5 days to investigate the pathological and immunological events of NiV infection leading to death. DC-SIGN-positive immature dendritic cells in tonsil and alveolar macrophages were identified at 3 days postinfection (DPI) as early targets of NiV, implicating their important role in the spread of NiV to other tissues. By 5 DPI, NiV spread to other tissues and cell types, including endothelium of medium caliber vessels and respiratory epithelium. Multifocal regions of fibrin deposition in small and medium caliber vessels and into alveolar spaces were also noted at 5 DPI. NiV antigen was not detected in cells of central nervous system tissues from any AGM at 3-5 DPI, indicating that neuroinvasion is a late event in untreated primates. NiV infection elicited a biphasic host response characterized by early loss of anticoagulant factors followed by robust induction of interferon-stimulated cytokines, chemokines, and endothelial activation markers, revealing a tightly coupled inflammatory-coagulatory cascade underlying disease progression. RNA-seq analyses of tonsil and lung identified a robust, complement-driven immune response in tonsil but a muted, interferon-driven response in lung. The sequence of pathogenetic events identified here may provide insight into developing new therapeutic interventions and optimizing lead candidate antivirals.

ORGANISM(S): Chlorocebus aethiops

PROVIDER: GSE310471 | GEO | 2026/04/22

REPOSITORIES: GEO