Recognition of hepaciviruses by ficolins in different mammalian species

Ficolins are polymorphic liver-expressed pattern recognition receptors (PRRs) that contribute to the innate surveillance of virus infections, recognising carbohydrates such as N-acetyl glucosamine, which are components of glycoproteins found on the surface of different viruses. While human ficolin-2...

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Main Author: Adedeji, Yemisi Oluwatomi
Format: Thesis (University of Nottingham only)
Language:English
Published: 2020
Subjects:
Online Access:https://eprints.nottingham.ac.uk/63458/
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author Adedeji, Yemisi Oluwatomi
author_facet Adedeji, Yemisi Oluwatomi
author_sort Adedeji, Yemisi Oluwatomi
building Nottingham Research Data Repository
collection Online Access
description Ficolins are polymorphic liver-expressed pattern recognition receptors (PRRs) that contribute to the innate surveillance of virus infections, recognising carbohydrates such as N-acetyl glucosamine, which are components of glycoproteins found on the surface of different viruses. While human ficolin-2 has been demonstrated to bind and inhibit entry of hepatitis C virus (HCV) particles, the antiviral activity of ficolins found in other mammalian species is unknown. For the first time, recombinant mouse and non-human primate (NHP) ficolins were cloned, expressed and purified to determine their interaction with HCV and non-primate/Equine hepacivirus (NPHV/EqHV), and the impact on virus entry. HCV and EqHV have been recently reported as closely related within the hepacivirus genera (family Flaviviridae). This relatedness may provide insights on the potential use of EqHV as a model for the study of HCV. Both viruses encode two glycoproteins (E1 and E2), which are found on the surface of the viral envelope. These glycoproteins facilitate the entry into the host and are targets for host immune recognition molecules like ficolins. HCV and EqHV pseudoparticles (pp) were used to determine the neutralising ability of ficolins from different species. An EqHVpp model system for the investigation of entry and neutralisation of EqHV infection was created and validated. In this study, for the first time, the neutralisation of hepacivirus by non-human ficolins was assessed. These findings may provide better insight into the divergent evolution of these genes in mammals. It is possible that ficolins might serve as a future therapeutic anti-viral agent for hepaciviruses.
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language English
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spelling nottingham-634582025-02-28T15:04:59Z https://eprints.nottingham.ac.uk/63458/ Recognition of hepaciviruses by ficolins in different mammalian species Adedeji, Yemisi Oluwatomi Ficolins are polymorphic liver-expressed pattern recognition receptors (PRRs) that contribute to the innate surveillance of virus infections, recognising carbohydrates such as N-acetyl glucosamine, which are components of glycoproteins found on the surface of different viruses. While human ficolin-2 has been demonstrated to bind and inhibit entry of hepatitis C virus (HCV) particles, the antiviral activity of ficolins found in other mammalian species is unknown. For the first time, recombinant mouse and non-human primate (NHP) ficolins were cloned, expressed and purified to determine their interaction with HCV and non-primate/Equine hepacivirus (NPHV/EqHV), and the impact on virus entry. HCV and EqHV have been recently reported as closely related within the hepacivirus genera (family Flaviviridae). This relatedness may provide insights on the potential use of EqHV as a model for the study of HCV. Both viruses encode two glycoproteins (E1 and E2), which are found on the surface of the viral envelope. These glycoproteins facilitate the entry into the host and are targets for host immune recognition molecules like ficolins. HCV and EqHV pseudoparticles (pp) were used to determine the neutralising ability of ficolins from different species. An EqHVpp model system for the investigation of entry and neutralisation of EqHV infection was created and validated. In this study, for the first time, the neutralisation of hepacivirus by non-human ficolins was assessed. These findings may provide better insight into the divergent evolution of these genes in mammals. It is possible that ficolins might serve as a future therapeutic anti-viral agent for hepaciviruses. 2020-12-31 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/63458/1/Yemisi%20O%20Adedeji_14225062.pdf Adedeji, Yemisi Oluwatomi (2020) Recognition of hepaciviruses by ficolins in different mammalian species. PhD thesis, University of Nottingham. HCV EqHV/NPHV Ficolins Innate immunity MBL Pseudoparticles Hepacivirus Protein expression Phylogentic tree Sequence analysis Ficolin-2 Non-human primate ficolin Fusion PCR ELISA Western blot Protein purification Pseudotype infectivity assay Pseudotyped based neutralisation assay Ficolin genes HCV model Antiviral therapy
spellingShingle HCV
EqHV/NPHV
Ficolins
Innate immunity
MBL
Pseudoparticles
Hepacivirus
Protein expression
Phylogentic tree
Sequence analysis
Ficolin-2
Non-human primate ficolin
Fusion PCR
ELISA
Western blot
Protein purification
Pseudotype infectivity assay
Pseudotyped based neutralisation assay
Ficolin genes
HCV model
Antiviral therapy
Adedeji, Yemisi Oluwatomi
Recognition of hepaciviruses by ficolins in different mammalian species
title Recognition of hepaciviruses by ficolins in different mammalian species
title_full Recognition of hepaciviruses by ficolins in different mammalian species
title_fullStr Recognition of hepaciviruses by ficolins in different mammalian species
title_full_unstemmed Recognition of hepaciviruses by ficolins in different mammalian species
title_short Recognition of hepaciviruses by ficolins in different mammalian species
title_sort recognition of hepaciviruses by ficolins in different mammalian species
topic HCV
EqHV/NPHV
Ficolins
Innate immunity
MBL
Pseudoparticles
Hepacivirus
Protein expression
Phylogentic tree
Sequence analysis
Ficolin-2
Non-human primate ficolin
Fusion PCR
ELISA
Western blot
Protein purification
Pseudotype infectivity assay
Pseudotyped based neutralisation assay
Ficolin genes
HCV model
Antiviral therapy
url https://eprints.nottingham.ac.uk/63458/