Aberrant PD-1 ligand expression contributes to the myocardial inflammatory injury caused by Coxsackievirus B infection
Aberrant PD-1 ligand expression contributes to the myocardial inflammatory injury caused by Coxsackievirus B infection
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PD-1配体表达异常导致柯萨奇B型病毒感染引起的心肌炎症损伤
DOI：
10.1016/j.antiviral.2019.03.007
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发表时间：
2019-06-01
影响因子：
7.6
通讯作者：
Zhong, Zhaohua
中科院分区：
文献类型：
--
作者：
Wang, Tianying;Chen, Shuang;Zhong, Zhaohua
柯萨奇病毒B组（CVB）是人类病毒性心肌炎最常见的病原体之一。CVB引起的心肌炎主要表现为持续的病毒感染和免疫介导的炎症损伤。共刺激信号对于适应性免疫的激活至关重要。我们的数据表明，CVB 3型（CVB 3）感染改变了宿主细胞中共刺激分子的表达谱。CVB 3感染引起PD-1配体表达减少，部分原因是病毒蛋白酶3C（pro）切割富含AU的元件结合蛋白AUF 1，导致心肌炎性损伤加重。此外，全身PD-L1治疗，增加了增殖淋巴细胞的凋亡，减轻了心肌炎性损伤。我们的研究结果表明，PD 1通路可能是一个潜在的免疫治疗CVB诱导的心肌炎的目标。
Coxsackievirus group B (CVB) is considered as one of the most common pathogens of human viral myocarditis. CVB-induced myocarditis is mainly characterized by the persistence of the virus infection and immune-mediated inflammatory injury. Costimulatory signals are crucial for the activation of adaptive immunity. Our data reveal that the CVB type 3 (CVB3) infection altered the expression profile of costimulatory molecules in host cells. CVB3 infection caused the decrease of PD-1 ligand expression, partially due to the cleavage of AU-rich element binding protein AUF1 by the viral protease 3C(pro), leading to the exacerbated inflammatory injury of the myocardium. Moreover, systemic PD-L1 treatment, which augmented the apoptosis of proliferating lymphocytes, alleviated myocardial inflammatory injury. Our findings suggest that PD1-pathway can be a potential immunologic therapeutic target for CVB-induced myocarditis.