Viruses are dependent on host cell metabolism and host cell factors to fulfil their replication cycle. In response cells have evolved multiple mechanisms to directly subvert viral replication. These mechanisms are an ancient form of cell intrinsic immunity. Many of these antiviral factors are interferon inducible and have immune signalling functions, and so are key components of the innate immune system.
Understanding how cellular antiviral factors function and how virus may overcome cellular antiviral inhibition is an area of much importance. This understanding can be harnessed therapeutically to yield novel therapeutic strategies based on the host-virus interaction.
Most antiviral restriction factors have a broad range of function against many unrelated virus types. How the innate immune system exerts such broad-spectrum antagonism is a key research interest of our lab. Understanding this may allow the development of broad-spectrum antiviral therapeutics. These would be of value against pandemic virus spread, emerging viral pathogens and neglected viral borne diseases.
Interferon induced transmembrane proteins (IFITMs) are of particular interest as IFITMs can antagonise the cellular entry of a number of clinically important viruses including influenza A virus, Ebola virus, Dengue virus, SARs coronavirus, Rift Valley fever virus, West Nile virus, and HIV. IFITMs and other functionally related antiviral factors seem to function by disrupting membrane lipid content. This seems to be an area of particular sensitivity to viruses, and so understanding the mechanistic basis of such antagonisms using retroviruses is a research priority for our group.