Longitudinal analysis of the antibody repertoire of a Zika virus-infected patient revealed dynamic changes in antibody response

The Zika virus (ZIKV) is a mosquito-borne flavivirus that causes neonatal abnormalities and other disorders. Antibodies to the ZIKV envelope (E) protein can block infection. In this study, next-generation sequencing (NGS) of immunoglobulin heavy chain (IgH) mRNA transcripts was combined with single-...

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Main Authors: Xuefeng Niu, Qihong Yan, Zhipeng Yao, Fan Zhang, Linbing Qu, Chunlin Wang, Chengrui Wang, Hui Lei, Chaoming Chen, Renshan Liang, Jia Luo, Qian Wang, Lingzhai Zhao, Yudi Zhang, Kun Luo, Longyu Wang, Hongkai Wu, Tingting Liu, Pingchao Li, Zhiqiang Zheng, Yee Joo Tan, Liqiang Feng, Zhenhai Zhang, Jian Han, Fuchun Zhang, Ling Chen
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2019.1701953
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author Xuefeng Niu
Qihong Yan
Zhipeng Yao
Fan Zhang
Linbing Qu
Chunlin Wang
Chengrui Wang
Hui Lei
Chaoming Chen
Renshan Liang
Jia Luo
Qian Wang
Lingzhai Zhao
Yudi Zhang
Kun Luo
Longyu Wang
Hongkai Wu
Tingting Liu
Pingchao Li
Zhiqiang Zheng
Yee Joo Tan
Liqiang Feng
Zhenhai Zhang
Jian Han
Fuchun Zhang
Ling Chen
author_facet Xuefeng Niu
Qihong Yan
Zhipeng Yao
Fan Zhang
Linbing Qu
Chunlin Wang
Chengrui Wang
Hui Lei
Chaoming Chen
Renshan Liang
Jia Luo
Qian Wang
Lingzhai Zhao
Yudi Zhang
Kun Luo
Longyu Wang
Hongkai Wu
Tingting Liu
Pingchao Li
Zhiqiang Zheng
Yee Joo Tan
Liqiang Feng
Zhenhai Zhang
Jian Han
Fuchun Zhang
Ling Chen
author_sort Xuefeng Niu
collection DOAJ
description The Zika virus (ZIKV) is a mosquito-borne flavivirus that causes neonatal abnormalities and other disorders. Antibodies to the ZIKV envelope (E) protein can block infection. In this study, next-generation sequencing (NGS) of immunoglobulin heavy chain (IgH) mRNA transcripts was combined with single-cell PCR cloning of E-binding monoclonal antibodies for analysing antibody response in a patient from the early stages of infection to more than one year after the clearance of the virus. The patient's IgH repertoire 14 and 64 days after symptom onset showed dramatic dominant clonal expansion but low clonal diversity. IgH repertoire 6 months after disease-free status had few dominant clones but increased diversity. E-binding antibodies appeared abundantly in the repertoire during the early stages of infection but quickly declined after clearance of the virus. Certain VH genes such as VH5-10-1 and VH4-39 appeared to be preferentially enlisted for a rapid antibody response to ZIKV infection. Most of these antibodies require relatively few somatic hypermutations to acquire the ability to bind to the E protein, pointing to a possible mechanism for rapid defence against ZIKV infection. This study provides a unique and holistic view of the dynamic changes and characteristics of the antibody response to ZIKV infection.
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publisher Taylor & Francis Group
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series Emerging Microbes and Infections
spelling doaj-art-14f58a7929fd4c4e8bb6231a56ed6c402025-08-20T03:08:32ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-019111112310.1080/22221751.2019.1701953Longitudinal analysis of the antibody repertoire of a Zika virus-infected patient revealed dynamic changes in antibody responseXuefeng Niu0Qihong Yan1Zhipeng Yao2Fan Zhang3Linbing Qu4Chunlin Wang5Chengrui Wang6Hui Lei7Chaoming Chen8Renshan Liang9Jia Luo10Qian Wang11Lingzhai Zhao12Yudi Zhang13Kun Luo14Longyu Wang15Hongkai Wu16Tingting Liu17Pingchao Li18Zhiqiang Zheng19Yee Joo Tan20Liqiang Feng21Zhenhai Zhang22Jian Han23Fuchun Zhang24Ling Chen25State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaGuangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People’s Republic of ChinaGuangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People’s Republic of ChinaGuangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People’s Republic of ChinaGuangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People’s Republic of ChinaHudsonAlpha Institute of Biotechnology, Huntsville, AL, USADepartment of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaState Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaGuangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People’s Republic of ChinaState Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaGuangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People’s Republic of ChinaGuangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People’s Republic of ChinaGuangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaGuangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People’s Republic of ChinaGuangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People’s Republic of ChinaGuangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People’s Republic of ChinaState Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaState Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaGuangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People’s Republic of ChinaDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore, SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore, SingaporeGuangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, People’s Republic of ChinaDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaHudsonAlpha Institute of Biotechnology, Huntsville, AL, USAGuangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaState Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaThe Zika virus (ZIKV) is a mosquito-borne flavivirus that causes neonatal abnormalities and other disorders. Antibodies to the ZIKV envelope (E) protein can block infection. In this study, next-generation sequencing (NGS) of immunoglobulin heavy chain (IgH) mRNA transcripts was combined with single-cell PCR cloning of E-binding monoclonal antibodies for analysing antibody response in a patient from the early stages of infection to more than one year after the clearance of the virus. The patient's IgH repertoire 14 and 64 days after symptom onset showed dramatic dominant clonal expansion but low clonal diversity. IgH repertoire 6 months after disease-free status had few dominant clones but increased diversity. E-binding antibodies appeared abundantly in the repertoire during the early stages of infection but quickly declined after clearance of the virus. Certain VH genes such as VH5-10-1 and VH4-39 appeared to be preferentially enlisted for a rapid antibody response to ZIKV infection. Most of these antibodies require relatively few somatic hypermutations to acquire the ability to bind to the E protein, pointing to a possible mechanism for rapid defence against ZIKV infection. This study provides a unique and holistic view of the dynamic changes and characteristics of the antibody response to ZIKV infection.https://www.tandfonline.com/doi/10.1080/22221751.2019.1701953Zika virusantibodyrepertoiremonoclonal antibodynext-generation sequencing
spellingShingle Xuefeng Niu
Qihong Yan
Zhipeng Yao
Fan Zhang
Linbing Qu
Chunlin Wang
Chengrui Wang
Hui Lei
Chaoming Chen
Renshan Liang
Jia Luo
Qian Wang
Lingzhai Zhao
Yudi Zhang
Kun Luo
Longyu Wang
Hongkai Wu
Tingting Liu
Pingchao Li
Zhiqiang Zheng
Yee Joo Tan
Liqiang Feng
Zhenhai Zhang
Jian Han
Fuchun Zhang
Ling Chen
Longitudinal analysis of the antibody repertoire of a Zika virus-infected patient revealed dynamic changes in antibody response
Emerging Microbes and Infections
Zika virus
antibody
repertoire
monoclonal antibody
next-generation sequencing
title Longitudinal analysis of the antibody repertoire of a Zika virus-infected patient revealed dynamic changes in antibody response
title_full Longitudinal analysis of the antibody repertoire of a Zika virus-infected patient revealed dynamic changes in antibody response
title_fullStr Longitudinal analysis of the antibody repertoire of a Zika virus-infected patient revealed dynamic changes in antibody response
title_full_unstemmed Longitudinal analysis of the antibody repertoire of a Zika virus-infected patient revealed dynamic changes in antibody response
title_short Longitudinal analysis of the antibody repertoire of a Zika virus-infected patient revealed dynamic changes in antibody response
title_sort longitudinal analysis of the antibody repertoire of a zika virus infected patient revealed dynamic changes in antibody response
topic Zika virus
antibody
repertoire
monoclonal antibody
next-generation sequencing
url https://www.tandfonline.com/doi/10.1080/22221751.2019.1701953
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