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Poxviruses package viral redox proteins in lateral bodies and modulate the host oxidative response

Bidgood, Susanna R; Samolej, Jerzy; Novy, Karel; Collopy, Abigail; Albrecht, David; Krause, Melanie; Burden, Jemima J; ... Mercer, Jason; + view all (2022) Poxviruses package viral redox proteins in lateral bodies and modulate the host oxidative response. PLOS Pathogens , 18 (7) , Article e1010614. 10.1371/journal.ppat.1010614. Green open access

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Abstract

All poxviruses contain a set of proteinaceous structures termed lateral bodies (LB) that deliver viral effector proteins into the host cytosol during virus entry. To date, the spatial proteotype of LBs remains unknown. Using the prototypic poxvirus, vaccinia virus (VACV), we employed a quantitative comparative mass spectrometry strategy to determine the poxvirus LB proteome. We identified a large population of candidate cellular proteins, the majority being mitochondrial, and 15 candidate viral LB proteins. Strikingly, one-third of these are VACV redox proteins whose LB residency could be confirmed using super-resolution microscopy. We show that VACV infection exerts an anti-oxidative effect on host cells and that artificial induction of oxidative stress impacts early and late gene expression as well as virion production. Using targeted repression and/or deletion viruses we found that deletion of individual LB-redox proteins was insufficient for host redox modulation suggesting there may be functional redundancy. In addition to defining the spatial proteotype of VACV LBs, these findings implicate poxvirus redox proteins as potential modulators of host oxidative anti-viral responses and provide a solid starting point for future investigations into the role of LB resident proteins in host immunomodulation.

Type: Article
Title: Poxviruses package viral redox proteins in lateral bodies and modulate the host oxidative response
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.ppat.1010614
Publisher version: https://doi.org/10.1371/journal.ppat.1010614
Language: English
Additional information: © 2022 Bidgood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10152267
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