Diagnostic differentiation of Zika and dengue virus exposure by analyzing T cell receptor sequences from peripheral blood of infected HLA-A2 transgenic mice.
Diagnostic differentiation of Zika and dengue virus exposure by analyzing T cell receptor sequences from peripheral blood of infected HLA-A2 transgenic mice.
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DOI：
10.1371/journal.pntd.0008896
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发表时间：
2020-12
影响因子：
3.8
通讯作者：
Pinto AK
中科院分区：
文献类型：
--
作者：
Hassert M;Wolf KJ;Rajeh A;Schiebout C;Hoft SG;Ahn TH;DiPaolo RJ;Brien JD;Pinto AK
寨卡病毒（ZIKV）是一种严重的全球健康威胁，因为它可能在怀孕期间感染时迅速出现并与严重的先天性畸形有关。尽管迫切需要，但ZIKV感染的准确诊断仍然是必须克服的主要障碍。导致ZIKV的大多数基于血清学的诊断测定的不准确性的是与其他黄病毒（包括登革病毒（DENV）的四种血清型）的大量地理和抗原重叠。在这项研究中，我们利用了一种新的T细胞受体（TCR）测序平台来区分ZIKV和DENV感染。使用从DENV和ZIKV感染的小鼠分离的淋巴细胞的高通量TCR测序，我们能够开发一种算法，其可以鉴定与小鼠中先前的ZIKV或DENV感染唯一相关的病毒相关TCR序列。使用这种算法，我们能够以97%的准确率分离暴露于ZIKV或DENV感染的小鼠。总的来说，这项研究作为一个原则证明，T细胞受体测序可以用作一种诊断工具，能够区分密切相关的病毒。我们的研究结果表明，这种创新平台有可能用于准确诊断寨卡病毒感染和潜在的下一个新兴病原体。由于血清学交叉反应性，登革热病毒和寨卡病毒感染之间的诊断区分是一个挑战。在这项研究中，我们使用了一种新的T细胞受体测序平台来鉴定与HLA-A2转基因小鼠中登革热或寨卡病毒感染显著相关的T细胞受体序列。这些文库用于计算训练诊断分类器，其能够在感染小鼠的独立队列中区分登革热和寨卡病毒。
Zika virus (ZIKV) is a significant global health threat due to its potential for rapid emergence and association with severe congenital malformations during infection in pregnancy. Despite the urgent need, accurate diagnosis of ZIKV infection is still a major hurdle that must be overcome. Contributing to the inaccuracy of most serologically-based diagnostic assays for ZIKV, is the substantial geographic and antigenic overlap with other flaviviruses, including the four serotypes of dengue virus (DENV). Within this study, we have utilized a novel T cell receptor (TCR) sequencing platform to distinguish between ZIKV and DENV infections. Using high-throughput TCR sequencing of lymphocytes isolated from DENV and ZIKV infected mice, we were able to develop an algorithm which could identify virus-associated TCR sequences uniquely associated with either a prior ZIKV or DENV infection in mice. Using this algorithm, we were then able to separate mice that had been exposed to ZIKV or DENV infection with 97% accuracy. Overall this study serves as a proof-of-principle that T cell receptor sequencing can be used as a diagnostic tool capable of distinguishing between closely related viruses. Our results demonstrate the potential for this innovative platform to be used to accurately diagnose Zika virus infection and potentially the next emerging pathogen(s). Diagnostic differentiation between dengue virus and Zika virus infections is a challenge due to serological cross-reactivity. In this study, we used a novel T cell receptor sequencing platform to identify T cell receptor sequences significantly associated with either dengue or Zika virus infection in HLA-A2 transgenic mice. These libraries were used to computationally train diagnostic classifiers which were capable of distinguishing between dengue and Zika virus in independent cohorts of infected mice.
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