8-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus.

Respiratory syncytial virus (RSV), along with other prominent respiratory RNA viruses such as influenza and SARS-CoV-2, significantly contributes to the global incidence of respiratory tract infections. These pathogens induce the production of reactive oxygen species (ROS), which play a crucial role...

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Main Authors: Lang Pan, Ke Wang, Wenjing Hao, Yaoyao Xue, Xu Zheng, Ritwika S Basu, Tapas K Hazra, Azharul Islam, Yashoda Hosakote, Bing Tian, Matthieu G Gagnon, Xueqing Ba, Istvan Boldogh
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-10-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1012616
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author Lang Pan
Ke Wang
Wenjing Hao
Yaoyao Xue
Xu Zheng
Ritwika S Basu
Tapas K Hazra
Azharul Islam
Yashoda Hosakote
Bing Tian
Matthieu G Gagnon
Xueqing Ba
Istvan Boldogh
author_facet Lang Pan
Ke Wang
Wenjing Hao
Yaoyao Xue
Xu Zheng
Ritwika S Basu
Tapas K Hazra
Azharul Islam
Yashoda Hosakote
Bing Tian
Matthieu G Gagnon
Xueqing Ba
Istvan Boldogh
author_sort Lang Pan
collection DOAJ
description Respiratory syncytial virus (RSV), along with other prominent respiratory RNA viruses such as influenza and SARS-CoV-2, significantly contributes to the global incidence of respiratory tract infections. These pathogens induce the production of reactive oxygen species (ROS), which play a crucial role in the onset and progression of respiratory diseases. However, the mechanisms by which viral RNA manages ROS-induced base oxidation remain poorly understood. Here, we reveal that 8-oxo-7,8-dihydroguanine (8-oxoGua) is not merely an incidental byproduct of ROS activity but serves as a strategic adaptation of RSV RNA to maintain genetic fidelity by hijacking the 8-oxoguanine DNA glycosylase 1 (OGG1). Through RNA immunoprecipitation and next-generation sequencing, we discovered that OGG1 binding sites are predominantly found in the RSV antigenome, especially within guanine-rich sequences. Further investigation revealed that viral ribonucleoprotein complexes specifically exploit OGG1. Importantly, inhibiting OGG1's ability to recognize 8-oxoGua significantly decreases RSV progeny production. Our results underscore the viral replication machinery's adaptation to oxidative challenges, suggesting that inhibiting OGG1's reading function could be a novel strategy for antiviral intervention.
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institution Kabale University
issn 1553-7366
1553-7374
language English
publishDate 2024-10-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Pathogens
spelling doaj-art-4fb7b110766a4feca2c22f32b1f192502024-11-28T05:31:03ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-10-012010e101261610.1371/journal.ppat.10126168-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus.Lang PanKe WangWenjing HaoYaoyao XueXu ZhengRitwika S BasuTapas K HazraAzharul IslamYashoda HosakoteBing TianMatthieu G GagnonXueqing BaIstvan BoldoghRespiratory syncytial virus (RSV), along with other prominent respiratory RNA viruses such as influenza and SARS-CoV-2, significantly contributes to the global incidence of respiratory tract infections. These pathogens induce the production of reactive oxygen species (ROS), which play a crucial role in the onset and progression of respiratory diseases. However, the mechanisms by which viral RNA manages ROS-induced base oxidation remain poorly understood. Here, we reveal that 8-oxo-7,8-dihydroguanine (8-oxoGua) is not merely an incidental byproduct of ROS activity but serves as a strategic adaptation of RSV RNA to maintain genetic fidelity by hijacking the 8-oxoguanine DNA glycosylase 1 (OGG1). Through RNA immunoprecipitation and next-generation sequencing, we discovered that OGG1 binding sites are predominantly found in the RSV antigenome, especially within guanine-rich sequences. Further investigation revealed that viral ribonucleoprotein complexes specifically exploit OGG1. Importantly, inhibiting OGG1's ability to recognize 8-oxoGua significantly decreases RSV progeny production. Our results underscore the viral replication machinery's adaptation to oxidative challenges, suggesting that inhibiting OGG1's reading function could be a novel strategy for antiviral intervention.https://doi.org/10.1371/journal.ppat.1012616
spellingShingle Lang Pan
Ke Wang
Wenjing Hao
Yaoyao Xue
Xu Zheng
Ritwika S Basu
Tapas K Hazra
Azharul Islam
Yashoda Hosakote
Bing Tian
Matthieu G Gagnon
Xueqing Ba
Istvan Boldogh
8-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus.
PLoS Pathogens
title 8-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus.
title_full 8-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus.
title_fullStr 8-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus.
title_full_unstemmed 8-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus.
title_short 8-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus.
title_sort 8 oxoguanine dna glycosylase1 conceals oxidized guanine in nucleoprotein associated rna of respiratory syncytial virus
url https://doi.org/10.1371/journal.ppat.1012616
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