INTRODUCTION The most severe form of dengue virus (DENV) illness, dengue haemorrhagic fever, is characterised by plasma leakage and increased vascular permeability. OBJECTIVES Given the critical role that endothelial cells play in the pathogenesis of DENV, we wanted to determine whether infection with DENV altered the expression of MHC class I related genes including HLA-E. RESULTS In this study, we provide evidence that HLA-E but not MICA/B or HLA-G is upregulated by all four serotypes of DENV in an endothelial cell line human microvascular endothelial cells (HMEC)-1. In contrast, Zika virus (ZIKV), a related flavivirus, where plasma leakage is not a major manifestation of disease, did not upregulate HLA-E. We found modest levels of soluble HLA-E in supernatants from DENV but not ZIKV-infected cells. Coculture experiments found minimal activation of natural killer (NK) cells in the presence of both uninfected and infected HMEC-1 cells. HLA-E induced by DENV infection could not dampen the degranulation of activated NK cells by interacting with its ligand NKG2a. CONCLUSIONS Our results suggest that while DENV infection induces HLA-E, the high MHC class I expression on uninfected and infected HMEC-1 cells may dominate the diverse signals generated between inhibitory and activating receptors on NK cells and ligands on target cells.

中文翻译：

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登革热而非寨卡病毒对 HLA-E 的上调。

引言 最严重的登革热病毒 (DENV) 疾病形式是登革出血热，其特征是血浆渗漏和血管通透性增加。目的 鉴于内皮细胞在 DENV 发病机制中的关键作用，我们想确定 DENV 感染是否会改变 MHC I 类相关基因（包括 HLA-E）的表达。结果 在本研究中，我们提供的证据表明，在内皮细胞系人微血管内皮细胞 (HMEC)-1 中，所有四种 DENV 血清型均上调 HLA-E 而不是 MICA/B 或 HLA-G。相比之下，寨卡病毒 (ZIKV) 是一种相关的黄病毒，血浆渗漏不是疾病的主要表现，但并未上调 HLA-E。我们在来自 DENV 的上清液中发现适度水平的可溶性 HLA-E，但在 ZIKV 感染的细胞中没有发现。共培养实验发现，在存在未感染和感染的 HMEC-1 细胞的情况下，自然杀伤 (NK) 细胞的激活最小。由 DENV 感染诱导的 HLA-E 不能通过与其配体 NKG2a 相互作用来抑制活化 NK 细胞的脱粒。结论 我们的研究结果表明，虽然 DENV 感染诱导 HLA-E，但未感染和感染的 HMEC-1 细胞上的高 MHC I 类表达可能主导 NK 细胞上的抑制性和激活性受体与靶细胞上的配体之间产生的各种信号。