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Title: Control of host innate immune (interferon) responses by Newcastle disease virus (NDV)
Author: Rasamanikkam, Manoja
ISNI:       0000 0004 7962 5205
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2019
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Newcastle disease virus (NDV) produces highly pathogenic disease in avian species and negatively impacts the poultry industry by infecting both domesticated and wild birds. Viral infections trigger antiviral innate immune responses by inducing expression of type I interferons (IFNs). NDV is a paramyxovirus, others of which are known to evade host innate immune response, especially the induction of, and/or signalling response to, type I IFNs by the actions of their accessory proteins. This study show that NDV infection does not induce chicken (ch) IFN1/2 and can block the production of chlFN1/2 induced by synthetic dsRNA poly (l:C) but not signalling pathway of chlFN induced by chIFN. Further evidence is provided to show that NDV-V accessory protein is responsible for this inhibition of chlFN1/2 induction. NDV-Vs from moderate and high virulence strains inhibited chlFN2 more significantly than the NDV-V protein of low virulence strain. Additional evidence is provided to show that the difference in the IFN2 antagonism seen between low and high virulence NDV-V proteins is due to three amino acids in the C- terminus of the NDV-V protein. NDV-V blocks IFN induction by directly or indirectly targeting multiple molecules involved in the induction pathway including chMDA5, chLGP2 and chlRF7. Only high virulence NDV-V had direct interaction with chMDA5; however, NDV-V from all four different strains antagonised chMDA5 activity in a strain- dependent manner. All NDV-V strains interacted with chLGP2, leading to the speculation that NDV-V indirectly antagonises chMDA5 activity through chLGP2. High virulence NDV-V also antagonised chlRF7 activity by direct interaction with chlRF7. These results shed new light on the inhibition of the chlFN system by NDV and understanding the molecular determinants behind these differences is essential for more effective control measures such as vaccine production and population screening. In addition this study also provided evidence that NDV-V protein might have a role in the production of viral progeny and in the overall fitness of the virus.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available