TY - JOUR
T1 - 8-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus
AU - Pan, Lang
AU - Wang, Ke
AU - Hao, Wenjing
AU - Xue, Yaoyao
AU - Zheng, Xu
AU - Basu, Ritwika
AU - Hazra, Tapas K.
AU - Islam, Azharul
AU - Hosakote Madaiah, Yashoda
AU - Tian, Bing
AU - Gagnon, Matthieu G.
AU - Ba, Xueqing
AU - Boldogh, Istvan
N1 - Publisher Copyright:
© 2024 Pan 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.
PY - 2024/10
Y1 - 2024/10
N2 - 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.
AB - 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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U2 - 10.1371/journal.ppat.1012616
DO - 10.1371/journal.ppat.1012616
M3 - Article
C2 - 39413143
AN - SCOPUS:85206522549
SN - 1553-7366
VL - 20
JO - PLoS pathogens
JF - PLoS pathogens
IS - 10
M1 - e1012616
ER -