Genome-wide characterization of alternative splicing in blood cells of COVID-19 and respiratory infections of relevance

Rui Huang; Wenbo Chen; Xueya Zhao; Yuefei Ma; Qiong Zhou; Junsen Chen; Muyi Zhang; Dingran Zhao; Yu Hou; Chunjiang He; Ying Wu

doi:10.1016/j.virs.2023.01.007

April 2023

. doi: 10.1016/j.virs.2023.01.007

Citation: Rui Huang, Wenbo Chen, Xueya Zhao, Yuefei Ma, Qiong Zhou, Junsen Chen, Muyi Zhang, Dingran Zhao, Yu Hou, Chunjiang He, Ying Wu. Genome-wide characterization of alternative splicing in blood cells of COVID-19 and respiratory infections of relevance .VIROLOGICA SINICA, 2023, 38(2) : 309-312. http://dx.doi.org/10.1016/j.virs.2023.01.007

新冠肺炎与相关呼吸道病原感染患者全血细胞中全基因组的选择性剪接特征

黄锐 ^a ,
陈文博 ^b ,
赵学雅 ^c ,
马跃飞 ^e ,
周琼 ^f ,
陈俊森 ^a ,
张慕一 ^a ,
赵丁燃 ^a ,
侯宇 ^d ,
何春江 ^b,, ,
吴莹 ^a,,

武汉大学泰康医学院医学病毒学研究所病毒学国家重点实验室和湖北省过敏与免疫学重点实验室, 武汉, 430072;中国武汉大学泰康医学院, 430071;重庆医科大学生命科学研究所, 中国重庆, 400016;华中科技大学同济医学院同济医院, 武汉, 430030;福建医科大学附属第一医院临床检验科, 福州, 350005;昆明医科大学公共卫生研究所, 中国昆明, 650500

通讯作者： 何春江, che@whu.edu.cn; 吴莹, yingwu@whu.edu.cn
收稿日期： 2022-07-14
录用日期： 2022-12-30

摘要

传染病可导致患者体内的可变剪接失调。然而，新冠患者体内可变剪切的全局性特征尚未阐明，新冠病毒感染和其他呼吸道病原感染之间的差异也未被研究。本研究下载了人类全血的公共RNA测序数据，并对新冠病毒和季节性冠状病毒感染患者以及流感和细菌性肺炎患者体内的可变剪接进行了全转录组分析。研究发现，新冠肺炎和其他呼吸道疾病在差异可变剪接事件（DASE）的类型、内含子片段的长度以及代谢、免疫和炎症等途径的富集方面表现出特异性和相似性。此外，本研究系统地探索了每种感染类型中与可变剪接事件相关的潜在RBP调节网络。一些特异性的和广谱性的RBPs和剪接因子，如ENOX1、CELF6，被认为与不同的感染高度相关。此外，细胞丰度和剪接事件的相关性分析表明，可变剪接在病原体感染期间细胞的丰度调节中起着重要作用。本研究表明，在人类全血样本中，不同呼吸道病原体感染引起的宿主转录反应和剪接程序有功能上的差异。此项研究对比了新冠肺炎和相关呼吸道感染性疾病中可变剪接的综合特征，这有利于我们理解在转录后水平上宿主细胞和呼吸道病原体之间的相互作用，为新的治疗方法提供了潜在靶点。
- 新型冠状病毒
- , 季节性冠状病毒
- , 流感
- , 细菌
- , 选择性剪接

Genome-wide characterization of alternative splicing in blood cells of COVID-19 and respiratory infections of relevance

Rui Huang ^a ,
Wenbo Chen ^b ,
Xueya Zhao ^c ,
Yuefei Ma ^e ,
Qiong Zhou ^f ,
Junsen Chen ^a ,
Muyi Zhang ^a ,
Dingran Zhao ^a ,
Yu Hou ^d ,
Chunjiang He ^b,, ,
Ying Wu ^a,,

a. State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Institute of Medical Virology, TaiKang Medical School, Wuhan University, Wuhan, 430072, China;
b. TaiKang Medical School, Wuhan University, Wuhan, 430071, China;
c. Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China;
d. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China;
e. Department of Clinical Laboratory, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China;
f. Public Health Institute of Kunming Medical University, Kunming, 650500, China

Corresponding author: Chunjiang He, che@whu.edu.cn Ying Wu, yingwu@whu.edu.cn
Received Date: 14 July 2022
Accepted Date: 30 December 2022

Abstract

Highlights
1. The first global exploration of alternative splicing changes in COVID-19 and relevant respiratory diseases
2. The specificities and similarities between alternative splicing events in different respiratory diseases
3. Identification of regulatory network of RBP and alternative splicing in respiratory diseases
4. Defining the interactions of alternative splicing and cell abundance in respiratory diseases

References
1. Ashraf U, Benoit-Pilven C, Lacroix V, Navratil V, Naffakh N. 2019. Advances in analyzing virus-induced alterations of host cell splicing. Trends Microbiol. 27, 268-281.
2. Bonenfant G, Meng R, Shotwell C, Badu P, Payne AF, Ciota AT, Sammons MA, Berglund JA, Pager CT. 2020. Asian Zika virus isolate significantly changes the transcriptional profile and alternative RNA splicing events in a neuroblastoma cell line. Viruses 12, 510.
3. Duriez M, Mandouri Y, Lekbaby B, Wang H, Schnuriger A, Redelsperger F, Guerrera CI, Lefevre M, Fauveau V, Ahodantin J, Quetier I, Chhuon C, Gourari S, Boissonnas A, Gill U, Kennedy P, Debzi N, Sitterlin D, Maini MK, Kremsdorf D, Soussan P. 2017. Alternative splicing of hepatitis B virus:A novel virus/host interaction altering liver immunity. J Hepatol. 67, 687-699.
4. Galbraith MD, Kinning KT, Sullivan KD, Baxter R, Araya P, Jordan KR, Russell S, Smith KP, Granrath RE, Shaw JR, Dzieciatkowska M, Ghosh T, Monte AA, D'Alessandro A, Hansen KC, Benett TD, Hsieh EW, Espinosa JM. 2021. Seroconversion stages COVID19 into distinct pathophysiological states. Elife 10, e65508.
5. julian.knight@well.ox.ac.uk CO-M-oBACEa, Consortium CO-M-oBA. 2022. A blood atlas of COVID-19 defines hallmarks of disease severity and specificity. Cell 185, 916-938.e958.
6. Kremsdorf D, Lekbaby B, Bablon P, Sotty J, Augustin J, Schnuriger A, Pol J, Soussan P. 2021. Alternative splicing of viral transcripts:The dark side of HBV. Gut 70, 2373-2382.
7. Lee Y, Rio DC. 2015. Mechanisms and regulation of alternative pre-mrna splicing. Annu Rev Biochem, 84:291-323.
8. Li D, Su M, Sun PP, Guo WP, Wang CY, Wang JL, Wang H, Zhang Q, Du LY, Xie GC. 2020. Global profiling of the alternative splicing landscape reveals transcriptomic diversity during the early phase of enterovirus 71 infection. Virology 548, 213-225.
9. Lin W, Zhu C, Hong J, Zhao L, Jilg N, Fusco DN, Schaefer EA, Brisac C, Liu X, Peng LF, Xu Q, Chung RT. 2015. The spliceosome factor SART1 exerts its anti-HCV action through mRNA splicing. J Hepatol, 62:1024-1032.
10. McClain MT, Constantine FJ, Henao R, Liu Y, Tsalik EL, Burke TW, Steinbrink JM, Petzold E, Nicholson BP, Rolfe R, Kraft BD, Kelly MS, Saban DR, Yu C, Shen X, Ko EM, Sempowski GD, Denny TN, Ginsburg GS, Woods CW. 2021. Dysregulated transcriptional responses to SARS-CoV-2 in the periphery. Nat Commun.12, 1079.
11. Pozzi B, Bragado L, Mammi P, Torti MF, Gaioli N, Gebhard LG, Garcia Sola ME, Vaz-Drago R, Iglesias NG, Garcia CC, Gamarnik AV, Srebrow A. 2020. Dengue virus targets RBM10 deregulating host cell splicing and innate immune response. Nucleic Acids Res. 48, 6824-6838.
12. Tomezsko PJ, Corbin VDA, Gupta P, Swaminathan H, Glasgow M, Persad S, Edwards MD, McIntosh L, Papenfuss AT, Emery A, Swanstrom R, Zang T, Lan TCT, Bieniasz P, Kuritzkes DR, Tsibris A, Rouskin S. 2020. Determination of RNA structural diversity and its role in HIV-1 rna splicing. Nature 582,438-442.
13. Wang LY, Balmat TJ, Antonia AL, Constantine FJ, Henao R, Burke TW, Ingham A, McClain MT, Tsalik EL, Ko ER, Ginsburg GS, DeLong MR, Shen XL, Woods CW, Hauser ER, Ko DC. 2021. An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility. Genome Medicine 13, 83.
14. Wu P, Chen D, Ding W, Wu P, Hou H, Bai Y, Zhou Y, Li K, Xiang S, Liu P, Ju J, Guo E, Liu J, Yang B, Fan J, He L, Sun Z, Feng L, Wang J, Wu T, Wang H, Cheng J, Xing H, Meng Y, Li Y, Zhang Y, Luo H, Xie G, Lan X, Tao Y, Li J, Yuan H, Huang K, Sun W, Qian X, Li Z, Huang M, Ding P, Wang H, Qiu J, Wang F, Wang S, Zhu J, Ding X, Chai C, Liang L, Wang X, Luo L, Sun Y, Yang Y, Zhuang Z, Li T, Tian L, Zhang S, Zhu L, Chang A, Chen L, Wu Y, Ma X, Chen F, Ren Y, Xu X, Liu S, Wang J, Yang H, Wang L, Sun C, Ma D, Jin X, Chen G. 2021. The trans-omics landscape of COVID-19. Nat Commun. 12, 4543.
15. Zheng HY, Xu M, Yang CX, Tian RR, Zhang M, Li JJ, Wang XC, Ding ZL, Li GM, Li XL, He YQ, Dong XQ, Yao YG, Zheng YT. 2020. Longitudinal transcriptome analyses show robust t cell immunity during recovery from COVID-19. Signal Transduct Target Ther. 5, 294.
Proportional views