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乙型肝炎病毒感染的肝细胞中,δ 型肝炎病毒作为一种免疫原性佐剂。

Hepatitis Delta Virus Acts as an Immunogenic Adjuvant in Hepatitis B Virus-Infected Hepatocytes.

机构信息

Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore, Singapore.

Singapore Immunology Network (SIgN), Agency of Science, Technology and Research (ASTAR), Singapore, Singapore.

出版信息

Cell Rep Med. 2020 Jul 21;1(4):100060. doi: 10.1016/j.xcrm.2020.100060.

Abstract

Hepatitis delta virus (HDV) requires hepatitis B virus (HBV) to complete its infection cycle and causes severe hepatitis, with limited therapeutic options. To determine the prospect of T cell therapy in HBV/HDV co-infection, we study the impact of HDV on viral antigen processing and presentation. Using models of HBV/HDV co-infection, we demonstrate that HDV boosts HBV epitope presentation, both in HBV/HDV co-infected and neighboring mono-HBV-infected cells through the upregulation of the antigen processing pathway mediated by IFN-β/λ. Liver biopsies of HBV/HDV patients confirm this upregulation. We then validate and in a HBV/HDV preclinical mouse model that HDV infection increases the anti-HBV efficacy of T cells with engineered T cell receptors. Thus, by unveiling the effect of HDV on HBV antigen presentation, we provide a framework to better understand HBV/HDV immune pathology, and advocate the utilization of engineered HBV-specific T cells as a potential treatment for HBV/HDV co-infection.

摘要

丁型肝炎病毒(HDV)需要乙型肝炎病毒(HBV)才能完成其感染周期,导致严重肝炎,治疗选择有限。为了确定 T 细胞治疗在 HBV/HDV 合并感染中的前景,我们研究了 HDV 对病毒抗原加工和呈递的影响。我们使用 HBV/HDV 合并感染模型,证明 HDV 通过 IFN-β/λ 介导的抗原加工途径的上调,增强了 HBV 表位的呈递,无论是在 HBV/HDV 合并感染细胞还是邻近的单 HBV 感染细胞中。HBV/HDV 患者的肝活检证实了这种上调。然后,我们验证并在 HBV/HDV 临床前小鼠模型中证明,HDV 感染增加了具有工程化 T 细胞受体的 T 细胞对乙型肝炎病毒的疗效。因此,通过揭示 HDV 对 HBV 抗原呈递的影响,我们为更好地理解 HBV/HDV 免疫病理学提供了一个框架,并提倡将工程化的乙型肝炎病毒特异性 T 细胞作为 HBV/HDV 合并感染的潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d565/7659593/edd2132f6d6b/fx1.jpg

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