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Updated: May 20, 2026
A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
Published on: April 28, 2019
A new model for Hendra virus encephalitis in the mouse
Johanna Dups1, Deborah Middleton, Manabu Yamada
1CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong, Australia.
Abstract:
Hendra virus (HeV) infection in humans is characterized by an influenza like illness, which may progress to pneumonia or encephalitis and lead to death. The pathogenesis of HeV infection is poorly understood, and the lack of a mouse model has limited the opportunities for pathogenetic research. In this project we reassessed the role of mice as an animal model for HeV infection and found that mice are susceptible to HeV infection after intranasal exposure, with aged mice reliably developing encephalitic disease. We propose an anterograde route of neuroinvasion to the brain, possibly along olfactory nerves. This is supported by evidence for the development of encephalitis in the absence of viremia and the sequential distribution of viral antigen along pathways of olfaction in the brain of intranasally challenged animals. In our studies mice developed transient lower respiratory tract infection without progressing to viremia and systemic vasculitis that is common to other animal models. These studies report a new animal model of HeV encephalitis that will allow more detailed studies of the neuropathogenesis of HeV infection, particularly the mode of viral spread and possible sequestration within the central nervous system; investigation of mechanisms that moderate the development of viremia and systemic disease; and inform the development of improved treatment options for human patients.
Insights
A new mouse model shows aged mice are susceptible to Hendra virus (HeV) infection via intranasal exposure, reliably developing encephalitis. This model aids research into HeV neuropathogenesis and potential treatments.
Area of Science:
- Veterinary Medicine
- Virology
- Neuroscience
Background:
- Hendra virus (HeV) infection in humans presents as influenza-like illness, potentially leading to fatal pneumonia or encephalitis.
- Understanding HeV pathogenesis is limited by the lack of suitable animal models.
- Previous research has not established mice as a reliable model for HeV infection.
Purpose of the Study:
- To reassess the utility of mice as an animal model for Hendra virus infection.
- To investigate the neuropathogenesis of HeV, focusing on routes of neuroinvasion.
- To establish a model for studying HeV encephalitis and informing treatment strategies.
Main Methods:
- Mice were intranasally exposed to Hendra virus.
- Susceptibility and disease progression were monitored, with a focus on aged mice.
- Viral antigen distribution and the presence of viremia were assessed.
- Respiratory and systemic disease markers were evaluated.
Main Results:
- Aged mice are susceptible to intranasal HeV infection, consistently developing encephalitis.
- Evidence suggests an anterograde route of neuroinvasion along olfactory pathways.
- Encephalitis developed in the absence of significant viremia or systemic vasculitis.
- Mice experienced transient lower respiratory tract infection.
Conclusions:
- A novel mouse model for HeV encephalitis has been established using intranasal exposure in aged mice.
- This model facilitates detailed studies on HeV neuropathogenesis, including viral spread within the central nervous system.
- The model will aid in investigating mechanisms controlling viremia and systemic disease, informing the development of improved treatments for human HeV infections.
