Characteristics of Norovirus capsid protein-specific CD8+ T-Cell responses in previously infected individuals.

IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Virulence Pub Date : 2024-12-01 Epub Date: 2024-05-29 DOI:10.1080/21505594.2024.2360133
Taojun He, Yilin Deng, Fang Zhang, Jin Zhang, Luhong Zhu, Qinjin Wang, Jie Ning, Hui Wu, Hanmei Yuan, Bin Li, Chao Wu
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Abstract

Norovirus (NV) infection causes acute gastroenteritis in children and adults. Upon infection with NV, specific CD8+ T cells, which play an important role in anti-infective immunity, are activated in the host. Owing to the NV's wide genotypic variability, it is challenging to develop vaccines with cross-protective abilities against infection. To aid effective vaccine development, we examined specific CD8+ T-cell responses towards viral-structural protein (VP) epitopes, which enable binding to host susceptibility receptors. We isolated peripheral blood mononuclear cells from 196 participants to screen and identify predominant core peptides towards NV main and small envelope proteins using ex vivo and in vitro intracellular cytokine staining assays. Human leukocyte antigen (HLA) restriction characteristics were detected using next-generation sequencing. Three conservative immunodominant VP-derived CD8+ T-cell epitopes, VP294-102 (TDAARGAIN), VP2153-161 (RGPSNKSSN), and VP1141-148 (FPHIIVDV), were identified and restrictively presented by HLA-Cw * 0102, HLA-Cw * 0702, and HLA-A *1101 alleles, separately. Our findings provide useful insights into the development of future vaccines and treatments for NV infection.

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既往感染者的诺罗病毒壳蛋白特异性 CD8+ T 细胞应答特征
诺如病毒(NV)感染会引起儿童和成人急性肠胃炎。感染诺如病毒后,宿主体内在抗感染免疫中发挥重要作用的特异性 CD8+ T 细胞会被激活。由于 NV 的基因型变异很大,因此开发具有交叉保护能力的疫苗具有挑战性。为了帮助有效开发疫苗,我们研究了针对病毒结构蛋白(VP)表位的特异性 CD8+ T 细胞反应,这些表位可与宿主易感受体结合。我们分离了 196 名参与者的外周血单核细胞,利用体外和体外细胞内细胞因子染色检测法筛选并确定了针对 NV 主包膜蛋白和小包膜蛋白的主要核心肽。利用新一代测序技术检测了人类白细胞抗原(HLA)的限制性特征。确定了三个保守的 VP 衍生 CD8+ T 细胞表位,即 VP294-102 (TDAARGAIN)、VP2153-161 (RGPSNKSSN) 和 VP1141-148 (FPHIIVDV),并分别由 HLA-Cw * 0102、HLA-Cw * 0702 和 HLA-A *1101 等位基因限制性呈现。我们的研究结果为未来开发 NV 感染疫苗和治疗方法提供了有益的启示。
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来源期刊
Virulence
Virulence IMMUNOLOGY-MICROBIOLOGY
CiteScore
9.20
自引率
1.90%
发文量
123
审稿时长
6-12 weeks
期刊介绍: Virulence is a fully open access peer-reviewed journal. All articles will (if accepted) be available for anyone to read anywhere, at any time immediately on publication. Virulence is the first international peer-reviewed journal of its kind to focus exclusively on microbial pathogenicity, the infection process and host-pathogen interactions. To address the new infectious challenges, emerging infectious agents and antimicrobial resistance, there is a clear need for interdisciplinary research.
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