Intracranial inoculation rapidly induces Nipah virus encephalitis in Syrian hamsters

Nipah virus (NiV) is a highly pathogenic Paramyxovirus associated with outbreaks in Malaysia, Bangladesh, and India with high mortality rates. NiV infection causes fatal respiratory and neurological disease. The majority of survivors suffer from long-term neurological sequelae or late onset and relapsed encephalitis. The pathogenesis of neurological disease is complex and has not been able to be studied in current animal models as they are skewed towards the development of lethal respiratory disease rather than neurological disease. Although NiV neurological disease can be observed in animal models, there is currently no model where the majority of animals consistently develop neurological disease. Here, we developed a new Syrian hamster (Mesocricetus auratus) model to mimic neurological disease in humans. Hamsters were inoculated intracranially in the cerebellomedullary cistern with different doses of NiV, strain Malaysia. Intracranial NiV inoculation in the cerebellomedullary cistern resulted in a rapid progression towards severe neurological disease requiring euthanasia. High Nipah viral loads were detected in the brains, and NiV spread from the CNS to the lungs. Histopathologic examination of the brain showed ischemic necrosis, often accompanied by marked edema and hemorrhage. NiV antigen was detected primarily in meninges and cerebellum, but rarely observed in brain parenchyma. These histological lesions were different from the typical lesions observed in NiV-infected humans. Thus, despite the consistent development of neurological disease, intracranial inoculation does not result in a model representative of NiV neurological disease.