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.
Highlights
Hendra virus (HeV) causes serious systemic infection with pneumonia and encephalitis in humans, horses and various laboratory animals [1,2,3,4]
We found that mice are susceptible to HeV infection when exposed via the intranasal route, but resist infection when challenged by a parenteral route
Aged and juvenile mice exposed by the subcutaneous route remained clinically well during the period of observation and at euthanasia there was no evidence of HeV infection by histology, immunohistochemistry or quantitative real-time polymerase chain reaction (qPCR) (Table 1)
Summary
Hendra virus (HeV) causes serious systemic infection with pneumonia and encephalitis in humans, horses and various laboratory animals [1,2,3,4]. It is a single-stranded, negative-sense RNA virus belonging to the family Paramyxoviridae and is classified within the genus Henipavirus which it shares with one other virus, Nipah virus (NiV). Since a further thirty four HeV outbreaks have been identified along the mid to north-eastern coast of Australia with infection of five more humans (of whom three died) and numerous horses [6,7,8,9]. There are as yet no readily available effective therapies or prophylaxis for HeV infection, either for use in humans or other susceptible animals
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