Structural basis for distinctive receptor tropism of emerging paramyxoviruses

Stelfox, A

Abstract:: A diverse array of viruses capable of infecting both humans and animals constitute the family Paramyxoviridae (Amarasinghe et al. 2019; Fields, Knipe, and Howley 2013). Concerns regarding the interspecies transmission potential paramyxoviruses harboured by wildlife reservoirs has motivated subsequent concerted viral surveillance efforts (Thibault et al. 2017; Drexler et al. 2012). Our understanding of many of these newly identified paramyxoviruses is primarily limited to genome in...
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APA Style

Stelfox, A. (2020). Structural basis for distinctive receptor tropism of emerging paramyxoviruses [PhD thesis]. University of Oxford.

MLA Style

Stelfox, A. Structural Basis for Distinctive Receptor Tropism of Emerging Paramyxoviruses. 2020. University of Oxford, PhD thesis.

Chicago Style

Stelfox, A. 2020. “Structural Basis for Distinctive Receptor Tropism of Emerging Paramyxoviruses.” PhD thesis, University of Oxford.
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Authors

+ Stelfox, A More by this author

Institution:: University of Oxford
Division:: MSD
Department:: NDM
Role:: Author

Contributors

+ Bowden, T

Role:: Supervisor

+ Engineering and Physical Sciences Research Council More from this funder

+ Nuffield Department of Medicine More from this funder

DOI:: 10.5287/ora-kom6j6gbo
Type of award:: DPhil
Level of award:: Doctoral
Awarding institution:: University of Oxford

Language:: English
Keywords:: structural biology

paramyxovirus

receptor-binding
Subjects:: virology

Biochemistry

molecular biology

structural biology
UUID:: uuid:19f79370-635e-4c05-a3e8-640698468c94
Deposit date:: 2020-01-29
ARK identifier:: ark:/29072/ora_19f79370635e4c05a3e8640698468c94

Related item:: A structure-based rationale for sialic acid independent host-cell entry of Sosuga virus
Description:: The bat-borne paramyxovirus, Sosuga virus (SosV), is one of many paramyxoviruses recently identified and classified within the newly established genus Pararubulavirus, family Paramyxoviridae. The envelope surface of SosV presents a receptor-binding protein (RBP), SosV-RBP, which facilitates host-cell attachment and entry. Unlike closely related hemagglutinin neuraminidase RBPs from other genera of the Paramyxoviridae, SosV-RBP and other pararubulavirus RBPs lack many of the stringently conserved residues required for sialic acid recognition and hydrolysis. We determined the crystal structure of the globular head region of SosV-RBP, revealing that while the glycoprotein presents a classical paramyxoviral six-bladed β-propeller fold and structurally classifies in close proximity to paramyxoviral RBPs with hemagglutinin-neuraminidase (HN) functionality, it presents a receptor-binding face incongruent with sialic acid recognition. Hemadsorption and neuraminidase activity analysis confirms the limited capacity of SosV-RBP to interact with sialic acid in vitro and indicates that SosV-RBP undergoes a nonclassical route of host-cell entry. The close overall structural conservation of SosV-RBP with other classical HN RBPs supports a model by which pararubulaviruses only recently diverged from sialic acid binding functionality.
Related item:: Cross-reactive and cross-neutralizing activity of human mumps antibodies against a novel mumps virus from bats
Description:: To evaluate the antigenic relationship between bat mumps virus (BMV) and the JL5 vaccine strain of mumps virus (MuVJL5), we rescued a chimeric virus bearing the F and HN glycoproteins of BMV in the background of a recombinant JL5 genome (rMuVJL5). Cross-reactivity and cross-neutralization between this chimeric recombinant MuV bearing the F and HN glycoproteins of BMV (rMuVJL5-F/HNBMV) virus and rMuVJL5 were demonstrated using hyperimmune mouse serum samples and a curated panel of human serum. All mouse and human serum samples that were able to neutralize rMuVJL5 infection had cross-neutralizing activity against rMuVJL5-F/HNBMV. Our data suggest that persons who have neutralizing antibodies against MuV might be protected from infection by BMV.

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Copyright holder:: Stelfox, A

Licence:: Terms and Conditions of Use for Oxford University Research Archive

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Structural basis for distinctive receptor tropism of emerging paramyxoviruses

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Structural basis for distinctive receptor tropism of emerging paramyxoviruses

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