The effect of mutations in the envelope protein of Zika virus on cellular tropism

Ruiz Jimenez, Fernando (2022) The effect of mutations in the envelope protein of Zika virus on cellular tropism. PhD thesis, University of Nottingham.

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Abstract

Zika virus infection arose as a public health issue during late 2015 and 2016 on the American continent. ZIKV epidemic was especially interesting since the previous report of patients infected by the virus only showed mild symptoms including fever, rash, and joint pain, however, the appearance of neurological symptoms including Guillain Barre syndrome in adults and microcephaly on new-borns and other clinical features that were grouped into Zika congenital syndrome. This change on the outcome of the infections resulted in many questions, what changed on the virus that favoured neuroinvasion? are these changes linked to mutations that suffered the virus? The envelope protein of the virus was the best candidate to try to explain the infection of neural cells and the later development of the reported syndromes since this is the first protein that interacts with the hosts' cells and changes in the amino acid sequence can lead to new interactions between the virus and the host.

In this study, experiments were designed to try to answer these questions, including identifying mutations on the envelope protein that had a direct impact on the cellular tropism. As a way to dissect the entry process and the interaction between the cells and the mutations on the glycoprotein, a pseudotype model was used. Different strategies were used to try to produce pseudotypes that incorporate the Zika protein including adjusting the amounts of backbone and heterologous glycoprotein, use different cell lines, and supplementing other viral proteins that could enhance particle production.

Other approaches were tested, including the generation of plasmids that contain the viral genome, viral production and harvest and the amplification of viral fragments to produce infectious viruses from PCR products. Altogether these experiments showed that the flaviviruses pose a challenge to the development of pseudo particles and other methodologies due to its replication cycle and the singularities of this viral family.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Ball, Jonathan
McClure, Patrick
Keywords: Zika, Pseudotypes, Infectivity, Mutations, Lenivitirus
Subjects: Q Science > QR Microbiology > QR355 Virology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 66711
Depositing User: Ruiz Jimenez, Fernando
Date Deposited: 31 Jul 2022 04:40
Last Modified: 31 Jul 2022 04:40
URI: http://eprints.nottingham.ac.uk/id/eprint/66711

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