Hendra virus (HeV) and Nipah virus (NiV) are henipaviruses that are highly pathogenic to a wide range of animals including humans, and are some of the few viruses from the Paramyxoviridae family with zoonotic ability. Pteropid fruit bats have been identified as the natural reservoir of HeV and NiV, with frequent fatal outbreaks occurring in Australia and Bangladesh, respectively.
Neuroinvasion leading to fatal encephalitis is a common outcome for human infections. Recently, we reported that when mice are exposed to HeV via the intranasal route, they consistently develop fatal encephalitis in addition to a transient lung infection. However, when challenged with Nipah virus, only the transient lung infection develops without encephalitis. This was an unexpected finding, as both HeV and NiV use the same host cell receptors, ephrin B2 and B3, for infection.
To understand this difference, reverse genetics is utilized to construct recombinant HeV with NiV protein counterparts. Within the biosafety level-4 (BSL-4) containment laboratory, these viruses are assessed for infection dynamics in murine cortical neuron cultures and in their ability to cause disease in the mouse model. To further characterize the mechanisms of neuronal spread, a range of drugs are used that are known to inhibit important pathways (e.g. microtubule assembly, cell entry inhibitors, nerve signal inhibitor). The role of these different pathways/interactions in HeV spread will then be assessed.
Determining the proteins and more specifically, key sequences that result in the neuronal phenotype will have a significant public health, social and economic impact as this may assist in future vaccine and therapeutic development for henipavirus infection and spread. Additionally, these key sequences could allow for rapid identification of paramyxovirus strains with neuroinvasive capabilities, resulting in the appropriate treatment and handling of those infected.