Whitehead, Thomas James; (2018) Characterisation of chicken interferon-inducible transmembrane proteins: locus architecture, gene expression and viral restriction. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Interferon-inducible transmembrane (IFITM) proteins are host cell derived restriction factors. Mammalian IFITM proteins have been shown to confer antiviral resistance when challenged with a diverse range of both enveloped and non-enveloped viruses. Little characterisation has been undertaken to date with the specific aim of elucidating their function and the antiviral properties of the chicken IFITM (chIFITM) gene family. The chIFITM gene family contains four genes located within a 17kb region on Gallus gallus chromosome 5. Currently there is little information available about the sequence diversity of these genes, their expression profiles or the role that they may play in restricting avian viral pathogens. Data presented in this thesis outlines a novel DNA pull-down sequencing technique which has allowed for the generation of a high quality contiguous reference sequence, alongside targeted sequencing of chicken cell lines and ex vivo cell cultures. Studies in this thesis have established that the chIFITMs are interferon stimulated and have characterized their upregulation in response to viral challenge with influenza A virus (IAV) in ovo, in vivo and in vitro, alongside other avian viruses. Stably-overexpressing DF-1 (immortalized chick embryo fibroblast) cells that express chIFITM1, 2, 3 and 3MUT (C71/71A) have been generated. These cell lines have been challenged with avian viruses including diverse strains of IAV and infectious bronchitis virus (IBV) and this data demonstrates that the chIFITMs are able to restrict avian viruses in vitro. Moreover, novel interactions have been identified which may help to uncover a possible mechanism of action. Global food security and protection of livestock from infectious agents remains a key priority, both in the United Kingdom and Internationally. This study examines the role of chIFITM proteins during viral infections and highlights one potential method of safeguarding the poultry industry, ensuring continuity of global food security.

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