Poster Presentation 12th Australasian Virology Society Meeting 2024

Advanced culture models and molecular tools to investigate filovirus pathogenesis (#148)

Joshua Deerain 1 , Sarah Edwards 1 , Alexander McAuley 1 , Manh Bang Tran 2 , Elizabeth Vincan 2 , Glenn Marsh 1
  1. Australian Centre for Disease Preparedness, CSIRO, Geelong, VIC, Australia
  2. Department of Infectious Diseases, University of Melbourne, Melbourne, VIC, Australia

Members within the family Filoviridae including Ebola virus and Marburg virus are recognised as significant zoonotic pathogens which pose significant risk to human and animal health. Data available from previous filovirus outbreaks suggest case fatality rates of >40% for some members. On the other hand, despite close genetic and evolutionary relationship, no disease has been observed in humans infected with Reston virus.

Understanding the underlying differences between these viruses and the drivers of disease is crucial not only for outbreak response but also for monitoring and preparedness for emerging viruses. This is particularly important in the context of Australia’s regional health security with evidence of circulating filoviruses in animals (primarily bats) widespread in the Asia-Pacific region.

To enhance our ability to investigate viral pathogenesis and prepare for future outbreaks, we have expanded our toolbox for filovirus research. Within the high-containment PC4 laboratories at ACDP, advanced 3D cell models including organ explants and stem-cell derived organoids have been established. These models accurately recapitulate the cellular organisation of human and animal tissues and have been demonstrated to support replication of various filoviruses. Additionally, we have developed a reverse genetic system to recover wild-type and recombinant viruses allowing us to explore genetic differences between filoviruses associated with different clinical outcomes.

Together, this work allows us to interrogate filovirus pathogenesis, providing critical information essential for assessing the risk posed by emerging filoviruses while simultaneously equipping us with tools to respond effectively to future outbreaks.