Identification of TRIM25 and ZAP as restriction factors of Arenaviruses through BioID-Derived proximity interactome analysis of Arenavirus NP

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Old, Finley Ellis Otterburn (2025) Identification of TRIM25 and ZAP as restriction factors of Arenaviruses through BioID-Derived proximity interactome analysis of Arenavirus NP. PhD thesis, University of Nottingham.

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Abstract

The Arenaviridae family of RNA viruses includes several important human pathogens, such as Lassa mammarenavirus (LASV), the causative agent of Lassa fever. A characteristic of arenavirus infection is the broad symptom range, from asymptomatic to fatal viral haemorrhagic fever. Understanding the mechanisms underlying this observed range in pathogenicity and symptoms is crucial to combatting the global health burden posed by human pathogenic arenaviruses.

This thesis aimed to identify host restriction factors of Old-World arenavirus nucleoproteins (NP) using BioID2 proximity labelling and to investigate their antiviral potential. Host interactomes for Lassa mammarenavirus, Lujo mammarenavirus and the non-human pathogenic Mopeia mammarenavirus NPs were generated. These highlighted critical immunological networks and conserved host proteins, including TRIM25 and Zinc antiviral protein (ZAP). Both of these host proteins were experimentally validated as potent restriction factors of arenavirus replication. Infection assays using a panel of TRIM25 mutants identified the SPRY domain of TRIM25 as essential for interaction with NP and effective viral replication inhibition. Structural studies utilising SEC-SAXS revealed distinct oligomerisation patterns between LASV, LUJV, and MOPV NP. Although challenges in protein purification hindered detailed characterisation of TRIM25 interactions, this research optimised methodologies for future investigations. These findings deepen the understanding of arenavirus-host interactions and identify key antiviral targets to inform therapeutic development.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Foster, Toshana
Campeotto, Ivan
Daly, Janet
Keywords: Arenaviridae; Arenavirus nucleoproteins; Arenavirus-host interactions; TRIM25; Zinc antiviral protein (ZAP)
Subjects: Q Science > QR Microbiology > QR355 Virology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Item ID: 81861
Depositing User: Old, Finley
Date Deposited: 10 Dec 2025 04:40
Last Modified: 10 Dec 2025 04:40
URI: https://eprints.nottingham.ac.uk/id/eprint/81861

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