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Title: Understanding Parechovirus pathogenesis through investigating IRES and cell receptor tropism
Author: Almalki, Shaia Saleh R.
ISNI:       0000 0004 5357 1966
Awarding Body: University of Essex
Current Institution: University of Essex
Date of Award: 2014
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Human parechovirus (HPeV) is a specIes, containing 16 types (HPeVI-I6), that belongs to the genus Parechovirus, a member of the Picornaviridae family. There is growing evidence that HPeVs are medically significant. They cause mild respiratory tract infection and gastroenteritis (mainly HPeV1 strains), or more serious illness such as eNS infection (mainly HPe V3 strains). This thesis describes work designed to improve our understanding of HPe V virulence, by analyzing the !RES (internal ribosome entry site) within the 5'UTR, and also cell receptor tropism. The IRES study included a comprehensive bioinformatic analysis of all picornaviruses that have a type II IRES and revealed novel relationships between structural domains in different viruses. The Human parechovirus 5'UTR was studied in detail and HPeV3-specific features were identified. A bicistronic construct was used to identify the significance of !RES domains in HPe V translation, and also showed that the IRES was not active in all cells lines used. Receptor tropism of several HPeV isolates was investigated by using blocking antibodies against integrins, previously reported to be receptors for the prototype HPeVI strain Harris. All the HPeVI isolates tested were blocked efficiently by the avB6 antibody, suggesting this is the key receptor for most HPe V isolates, although some blocking by the avB3 antibody was observed and this molecule could also be important. Two isolates were identified which probably use heparan sulphate as a coreceptor, as infection was blocked by heparin, and sequencing of these and non-blocked isolates identified an amino acid difference in VP1. This is probably the key amino acid involved in binding. Overall, the work has given new insights into HPeV molecular biology, which may ultimately allow us to understand how these viruses infect cells and cause disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available