Attenuated Duck Hepatitis A Virus Infection Is Associated With High mRNA Maintenance in Duckling Liver via m6A Modification

Host translation is generally modulated by viral infection, including duck hepatitis A virus (DHAV) infection. Previously, we reported that cellular protein synthesis in a cell model of duck embryo fibroblasts is significantly inhibited by DHAV infection but not viral proteins, suggesting that an im...

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Main Authors: Liping Wu, Weili Quan, Yi Zhang, Mingshu Wang, Xumin Ou, Sai Mao, Di Sun, Qiao Yang, Ying Wu, Yaxun Wei, Renyong Jia, Shun Chen, Dekang Zhu, Mafeng Liu, Xinxin Zhao, Shaqiu Zhang, Juan Huang, Qun Gao, Bin Tian, Anchun Cheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.839677/full
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author Liping Wu
Weili Quan
Yi Zhang
Mingshu Wang
Xumin Ou
Sai Mao
Di Sun
Qiao Yang
Ying Wu
Yaxun Wei
Renyong Jia
Shun Chen
Dekang Zhu
Mafeng Liu
Xinxin Zhao
Shaqiu Zhang
Juan Huang
Qun Gao
Bin Tian
Anchun Cheng
author_facet Liping Wu
Weili Quan
Yi Zhang
Mingshu Wang
Xumin Ou
Sai Mao
Di Sun
Qiao Yang
Ying Wu
Yaxun Wei
Renyong Jia
Shun Chen
Dekang Zhu
Mafeng Liu
Xinxin Zhao
Shaqiu Zhang
Juan Huang
Qun Gao
Bin Tian
Anchun Cheng
author_sort Liping Wu
collection DOAJ
description Host translation is generally modulated by viral infection, including duck hepatitis A virus (DHAV) infection. Previously, we reported that cellular protein synthesis in a cell model of duck embryo fibroblasts is significantly inhibited by DHAV infection but not viral proteins, suggesting that an important viral-host interaction occurs at the translational level. In this study, we aim to further understand the impact of DHAV virulence on cellular N6-methyladenosine (m6A) modification, which is essential to a wide variety of RNA biological processes, such as mRNA stabilization and translation. Using m6A antibody-based immunoprecipitation, m6A-seq, and LC–MS/MS, we observed that m6A-modified mRNA exists in both virulent and attenuated DHAV-infected duckling livers. Importantly, m6A levels in mRNA were much higher in attenuated DHAV-infected livers compared with virulent DHAV-infected livers, suggesting virulence-dependent regulation of m6A modification. Analysis of modification motifs indicated that GAAGAAG is the most enriched motif. Combined m6A-seq and RNA-seq data analysis indicated a generally positive correlation between m6A and mRNA expression levels in DHAV-infected duckling livers. GO analysis of genes with decreased or increased m6A levels showed that these genes were enriched in various terms, including oxidation–reduction processes and antiviral immune responses. Collectively, our work reveals DHAV virulence-dependent coordination between m6A modification and mRNA expression in duckling livers.
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spelling doaj.art-2e63dcb64152489ea22cf2e26e8fb1f42022-12-22T00:58:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.839677839677Attenuated Duck Hepatitis A Virus Infection Is Associated With High mRNA Maintenance in Duckling Liver via m6A ModificationLiping Wu0Weili Quan1Yi Zhang2Mingshu Wang3Xumin Ou4Sai Mao5Di Sun6Qiao Yang7Ying Wu8Yaxun Wei9Renyong Jia10Shun Chen11Dekang Zhu12Mafeng Liu13Xinxin Zhao14Shaqiu Zhang15Juan Huang16Qun Gao17Bin Tian18Anchun Cheng19Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaABLife BioBigData Institute, Wuhan, ChinaABLife BioBigData Institute, Wuhan, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCenter for Genome Analysis, ABLife, Inc., Wuhan, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaInstitute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaHost translation is generally modulated by viral infection, including duck hepatitis A virus (DHAV) infection. Previously, we reported that cellular protein synthesis in a cell model of duck embryo fibroblasts is significantly inhibited by DHAV infection but not viral proteins, suggesting that an important viral-host interaction occurs at the translational level. In this study, we aim to further understand the impact of DHAV virulence on cellular N6-methyladenosine (m6A) modification, which is essential to a wide variety of RNA biological processes, such as mRNA stabilization and translation. Using m6A antibody-based immunoprecipitation, m6A-seq, and LC–MS/MS, we observed that m6A-modified mRNA exists in both virulent and attenuated DHAV-infected duckling livers. Importantly, m6A levels in mRNA were much higher in attenuated DHAV-infected livers compared with virulent DHAV-infected livers, suggesting virulence-dependent regulation of m6A modification. Analysis of modification motifs indicated that GAAGAAG is the most enriched motif. Combined m6A-seq and RNA-seq data analysis indicated a generally positive correlation between m6A and mRNA expression levels in DHAV-infected duckling livers. GO analysis of genes with decreased or increased m6A levels showed that these genes were enriched in various terms, including oxidation–reduction processes and antiviral immune responses. Collectively, our work reveals DHAV virulence-dependent coordination between m6A modification and mRNA expression in duckling livers.https://www.frontiersin.org/articles/10.3389/fimmu.2022.839677/fullduck hepatitis A virusm6A modificationliverduck viral hepatitisvirulence
spellingShingle Liping Wu
Weili Quan
Yi Zhang
Mingshu Wang
Xumin Ou
Sai Mao
Di Sun
Qiao Yang
Ying Wu
Yaxun Wei
Renyong Jia
Shun Chen
Dekang Zhu
Mafeng Liu
Xinxin Zhao
Shaqiu Zhang
Juan Huang
Qun Gao
Bin Tian
Anchun Cheng
Attenuated Duck Hepatitis A Virus Infection Is Associated With High mRNA Maintenance in Duckling Liver via m6A Modification
Frontiers in Immunology
duck hepatitis A virus
m6A modification
liver
duck viral hepatitis
virulence
title Attenuated Duck Hepatitis A Virus Infection Is Associated With High mRNA Maintenance in Duckling Liver via m6A Modification
title_full Attenuated Duck Hepatitis A Virus Infection Is Associated With High mRNA Maintenance in Duckling Liver via m6A Modification
title_fullStr Attenuated Duck Hepatitis A Virus Infection Is Associated With High mRNA Maintenance in Duckling Liver via m6A Modification
title_full_unstemmed Attenuated Duck Hepatitis A Virus Infection Is Associated With High mRNA Maintenance in Duckling Liver via m6A Modification
title_short Attenuated Duck Hepatitis A Virus Infection Is Associated With High mRNA Maintenance in Duckling Liver via m6A Modification
title_sort attenuated duck hepatitis a virus infection is associated with high mrna maintenance in duckling liver via m6a modification
topic duck hepatitis A virus
m6A modification
liver
duck viral hepatitis
virulence
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.839677/full
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