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Title: Control of host innate immune (interferon) responses by peste des petits ruminants virus (PPRV)
Author: Sanz Bernardo, Beatriz
ISNI:       0000 0004 6061 0070
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2015
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Abstract:
Peste des petits ruminants virus (PPRV) produces clinical disease in goats and sheep. PPRV is a morbillivirus, others of which are known to affect the activation of the innate immune response by the actions of their accessory proteins (V&C). A crucial part of normal activation is the induction of interferon β (IFNβ) after pathogen recognition by pattern recognition receptors (PRRs). The presence of viral RNA can be sensed by the cytosolic proteins MDA-5 and RIG-I, starting a signalling cascade that leads to the activation of the IFNβ promoter and the synthesis of IFNβ. The production of IFNβ is a defence mechanism to control the spread of infection to neighbouring cells. Many viruses have evolved to antagonize this cell response. In this thesis I present a study of the induction of IFNβ following PPRV infection in both goat and primate cells, and the effects of infection with PPRV on the induction of IFNβ following MDA-5 and RIG-I mediated activation. Using both reporter assays and direct measurement of IFNβ mRNA, I found that PPRV infection does not induce IFNβ and can block the activation of expression of IFNβ. A study of the interaction of the PPRV accessory proteins with MDA-5 and RIG-I was carried out, including the cloning of goat RIG-I and LGP2. I also generated mutant viruses that lack expression of either accessory protein to characterize the role of these proteins in IFNβ induction during virus infection. Overexpression of V blocks MDA-5 mediated induction of IFNβ, but PPRV lacking V can still block MDA-5 mediated activation of IFNβ. PPRV C bound to neither MDA-5 nor RIG-I, but PPRV lacking C lost the ability to block MDA-5 and RIG-I mediated activation of IFNβ. These results shed new light on the inhibition of the induction of IFNβ by PPRV.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.703281  DOI: Not available
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