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

对寨卡病毒感染患者的抗体库进行纵向分析,揭示了抗体反应的动态变化

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作者: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

Abstract

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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