Influenza A Virus PB1-F2 Protein: a Putative Virulence Factor and Initiator of Inflammation

Project Details

Dr McAuley is currently interested in understanding mechanisms of virulence of influenza virus and host strategies to combat infection. She aims to further explore the mechanisms to which the influenza virus PB1-F2 protein contributes to pathogenesis and to identify key features that may enable prediction of severity of disease in novel influenza outbreaks.

Influenza A virus (IAV) is associated with substantial morbidity and mortality and not only poses a constant threat due to emergence of new virus strains of unknown virulence in winter epidemics but can also trigger pandemics with the potential for deaths in the millions. No one can predict the severity of any influenza season, including a pandemic season. The three IAVs that caused separate pandemics in the 20th century and the 2009 H1N1 pandemic virus vary widely in their virulence. Likewise seasonal IAV outbreaks can differ in their severity. Understanding factors contributing to IAV virulence is paramount if we are to ameliorate disease burden. The IAV PB1-F2 protein contributes to pathogenesis. Modified laboratory IAV strains producing PB1-F2 protein of lethal pandemic isolates enhances inflammation in the mouse model of infection, while pandemic 2009 H1N1 derived PB1-F2 protein does not. A clearer understanding of the host mechanisms of inflammation that PB1-F2 protein activates is currently being explored. Additionally, PB1-F2 proteins from relevant pandemic, epidemic and seasonal isolates are being evaluated for their influence on disease status during infection.

Researchers

Robert Allen: PhD student
Charley Mackenzie-Kludas: Research Assistant

Collaborators

Dr Jonathan McCullers, Dept Infectious Diseases, St Jude Children's Research Hospital, USA; Prof Anne Kelso (WHO), Dr Ashley Mansell, Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research

Funding

NH&MRC New Investigator Project Grant "The impact of influenza A virus PB1-F2 protein on host immunity and the potential for therapeutic targeting"
The project aims to explore the host-specific pathways triggered by expression of PB1-F2 during IAV infection and correlate these outcomes with the enhanced inflammatory responses observed in the host in previous work.

Research Group

Brown laboratory: Immunology; virology; vaccinology



Faculty Research Themes

Infection and Immunology

School Research Themes

Infection & Immunity, Molecular Mechanisms of Disease



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Microbiology and Immunology