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133539 - Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production.pdf (8.96 MB)

Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production

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journal contribution
posted on 2023-05-20, 05:02 authored by Hu, M, Schulze, KE, Ghildyal, R, Darren HenstridgeDarren Henstridge, Kolanowski, JL, New, EJ, Hong, Y, Hsu, AC, Hansbro, PM, Wark, PAB, Bogoyevitch, MA, Jans, DA
Although respiratory syncytial virus (RSV) is responsible for more human deaths each year than influenza, its pathogenic mechanisms are poorly understood. Here high-resolution quantitative imaging, bioenergetics measurements and mitochondrial membrane potential- and redox-sensitive dyes are used to define RSV’s impact on host mitochondria for the first time, delineating RSV-induced microtubule/dynein-dependent mitochondrial perinuclear clustering, and translocation towards the microtubule-organizing centre. These changes are concomitant with impaired mitochondrial respiration, loss of mitochondrial membrane potential and increased production of mitochondrial reactive oxygen species (ROS). Strikingly, agents that target microtubule integrity the dynein motor protein, or inhibit mitochondrial ROS production strongly suppresses RSV virus production, including in a mouse model with concomitantly reduced virus- induced lung inflammation. The results establish RSV’s unique ability to co-opt host cell mitochondria to facilitate viral infection, revealing the RSV-mitochondrial interface for the first time as a viable target for therapeutic intervention.

History

Publication title

eLife

Volume

8

Pagination

e42448

ISSN

2050-084X

Department/School

School of Health Sciences

Publisher

eLife Sciences Publications Ltd.

Place of publication

United Kingdom

Rights statement

Copyright 2019 Hu et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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