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Biophysical characterisation of the involvement of influenza A virus glycoproteins in receptor binding

Benton, DJ; (2015) Biophysical characterisation of the involvement of influenza A virus glycoproteins in receptor binding. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Influenza A viruses (IAV) cause human infections in both seasonal and pandemic forms, which are responsible for significant levels of human infections. A major factor underlying IAV viral fitness and transmissibility, and therefore pandemic potential, is the interaction of the virus with the cell surface, which is mediated by the two surface glycoproteins haemagglutinin (HA) and neuraminidase (NA). These two glycoproteins have antagonistic activities with the HA responsible for receptor binding and the NA for receptor destroying activities. It has long been hypothesised that the balance between these antagonistic functions is important in altering virus fitness and transmissibility. This thesis presents a new biophysical approach, based on biolayer interferometry, for determining the relative importance of the HA and NA in altering virus binding to a receptor coated surface. These experiments identified a number of fundamental characteristics of virus attachment and interaction with surfaces. This new technique has also been used to examine two other lineages of viruses that are at different stages of becoming transmissible in humans. H7N9 viruses first infected humans in 2013 and have caused a large number of zoonotic infections. The receptor binding characteristics of these H7N9 viruses are characterised with a particular focus on the NA, as N9 NAs have been previously shown to have receptor binding properties. In 2009 a new H1N1 pandemic emerged, which was formed from a reassortment of two swine viruses. These new viruses had acquired a number of substitutions in the HA, which could affect receptor binding, also the combination of HA and NA was also novel. A number of HA mutants and combinations of HA and NA were examined in terms of receptor binding in an attempt to understand what changes in swine viruses might make them transmissible in humans.

Type: Thesis (Doctoral)
Title: Biophysical characterisation of the involvement of influenza A virus glycoproteins in receptor binding
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1473702
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