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Human Paramyxovirus Infections Induce T Cells That Cross-React with Zoonotic Henipaviruses.
mBio ( IF 6.4 ) Pub Date : 2020-07-07 , DOI: 10.1128/mbio.00972-20
Rory D de Vries 1 , Alwin de Jong 1 , R Joyce Verburgh 1 , Lucie Sauerhering 2 , Gijsbert P van Nierop 1 , Robert S van Binnendijk 3 , Albert D M E Osterhaus 1 , Andrea Maisner 2 , Marion P G Koopmans 1 , Rik L de Swart 4
Affiliation  

Humans are infected with paramyxoviruses of different genera early in life, which induce cytotoxic T cells that may recognize conserved epitopes. This raises the question of whether cross-reactive T cells induced by antecedent paramyxovirus infections provide partial protection against highly lethal zoonotic Nipah virus infections. By characterizing a measles virus-specific but paramyxovirus cross-reactive human T cell clone, we discovered a highly conserved HLA-B*1501-restricted T cell epitope in the fusion protein. Using peptides, tetramers, and single cell sorting, we isolated a parainfluenza virus-specific T cell clone from a healthy adult and showed that both clones cleared Nipah virus-infected cells. We identified multiple conserved hot spots in paramyxovirus proteomes that contain other potentially cross-reactive epitopes. Our data suggest that, depending on HLA haplotype and history of paramyxovirus exposures, humans may have cross-reactive T cells that provide protection against Nipah virus. The effect of preferential boosting of these cross-reactive epitopes needs to be further studied in light of paramyxovirus vaccination studies.

中文翻译:

人副粘病毒感染会诱导与人畜共患性肝炎病毒交叉反应的T细胞。

人类在生命的早期就感染了不同属的副粘病毒,它们会诱导可能识别保守表位的细胞毒性T细胞。这就提出了一个问题,即由先前的副粘病毒感染引起的交叉反应性T细胞是否提供了针对高度致死的人畜共患的尼帕病毒感染的部分保护作用。通过表征麻疹病毒特异性但副粘病毒交叉反应的人T细胞克隆,我们发现了融合蛋白中高度保守的HLA-B * 1501限制性T细胞表位。使用肽,四聚体和单细胞分选,我们从健康的成年人中分离了副流感病毒特异性T细胞克隆,并显示这两个克隆均清除了Nipah病毒感染的细胞。我们在副粘病毒蛋白质组中发现了多个保守的热点,其中包含其他潜在的交叉反应性抗原决定簇。我们的数据表明,根据HLA单倍型和副粘病毒暴露史,人类可能具有交叉反应性T细胞,可提供针对Nipah病毒的保护。需要根据副粘病毒疫苗接种研究进一步研究优先增强这些交叉反应性表位的作用。
更新日期:2020-08-25
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