Influenza A virus (IAV) causes major epidemic and pandemic outbreaks in humans and important livestock species such as pigs and chickens. The flow of IAV between poultry, pigs and humans underlies pandemic outbreaks by aiding exchange of genetic material between viruses adapted to these species. However, the occurrence of viral jumps from one species to another is relatively rare due to the difficulty of adapting to a new species.
The host interferon (IFN) response represents a major barrier to this occurring. Interferon (IFN) is an important early host defence to viral infections. The evolutionary differences in host IFN response in different species represents a major barrier to zoonotic and epizootic IAV infection and adaptation. We are interested in determining how these differences contribute to the barriers in zoonotic spread and how IAV adapts to overcome these barriers, potentially leading to dangerous pandemic outbreaks.
Systematic analysis using arrayed Interferon Stimulated Gene (ISG) expression libraries have proven a powerful method for identifying key components of the IFN response in human cells [1-3]. However, such libraries are not available for pig and chicken, limiting our understanding of the species-specific differences in response and susceptibility to infection.
Our group aims to bridge the gap in systematic approaches in livestock species by developing cutting edge tools for high throughput screens. We have recently developed genome-wide CRISPR Cas9 knockout libraries for pig and chicken and have secured funding for the generation of ISG libraries in the same species. We aim to use these tools to dissect the role of the IFN factors during zoonotic spread of IAV.
The project aims to identify and characterise species-specific novel host-virus interactions and by comparing screen data between humans, pigs and chickens, further our understanding of the molecular processes involved in zoonotic viral spread.
In addition to gaining a solid foundation in core molecular virology techniques, such as DNA cloning, tissue culture, virus culture, western blotting and PCR/RT-PCR, the project offers the opportunity to gain experience and expertise in cutting-edge, high throughput approaches such as CRISPR-Cas9 gene editing and arrayed lentiviral expression library screening, with results having potentially important implications for our understanding of pandemic IAV outbreaks in humans and animals.
1 Dittmann, M. et al. A serpin shapes the extracellular environment to prevent influenza A virus maturation. Cell 160, 631-643, doi:10.1016/j.cell.2015.01.040 (2015).
2 Kane, M. et al. Identification of Interferon-Stimulated Genes with Antiretroviral Activity. Cell host & microbe 20, 392-405, doi:10.1016/j.chom.2016.08.005 (2016).
3 Schoggins, J. W. et al. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 472, 481-485, doi:10.1038/nature09907 (2011).