Poster Presentation 8th Australasian Virology Society Meeting and 11th Annual Meeting of the Australian Centre for Hepatitis & HIV Virology Meeting 2015

Subclinical Hendra virus encephalitis with late-onset neurological disease in mice (#119)

Bronwyn A Clayton 1 , Deborah Middleton 1 , Mary Tachedjian 1 , Leah Frazer 1 , Linfa Wang 2 , Glenn A Marsh 1
  1. Health and Biosecurity, Australian Animal Health Laboratory, CSIRO, East Geelong, VIC, Australia
  2. Program on Emerging Infectious Disease, Duke-NUS Graduate Medical School, Singapore

Hendra virus (HeV) is a Biosafety level-4 (BSL-4) zoonotic agent that induces overwhelming infection with high mortality rate in naturally-infected horses and people. Of seven cases of human HeV infection, one survivor had significant neurological sequelae following acute encephalitis; two died of acute encephalitis; and a fourth developed brief aseptic meningitis and then severe, fatal encephalitis after 13 months. In the current time course study, ninety-six mice were intranasally exposed to HeV and euthanased at intervals for up to 6 months to evaluate the HeV infection status of the brain after the acute infection phase. Twenty-six mice met a case definition for chronic subclinical HeV encephalitis, namely HeV RNA and antigen in brain, histological evidence of encephalitis, and serum antibody to the HeV G protein in a clinically normal mouse at least 21 days post-exposure to HeV. Three mice exhibited late-onset clinical encephalitis, defined by the above criteria but with signs of neurological disease. Whole genome sequencing was conducted on brain tissue of selected mice to evaluate whether virus with the potential to produce an infectious particle persisted in these animals. Mice are the only animal species that can feasibly be held over lifespan under BSL-4 containment conditions, and the mouse model for persistent and late-onset HeV encephalitis will be an invaluable tool for further study of the neuropathogenesis of HeV infection and its control.