An hepatitis B and D virus infection model using human pluripotent stem cell-derived hepatocytes.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Reports Pub Date : 2024-10-01 Epub Date: 2024-09-04 DOI:10.1038/s44319-024-00236-0

Huanting Chi, Bingqian Qu, Angga Prawira, Talisa Richardt, Lars Maurer, Jungen Hu, Rebecca M Fu, Florian A Lempp, Zhenfeng Zhang, Dirk Grimm, Xianfang Wu, Stephan Urban, Viet Loan Dao Thi

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Abstract

Current culture systems available for studying hepatitis D virus (HDV) are suboptimal. In this study, we demonstrate that hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) are fully permissive to HDV infection across various tested genotypes. When co-infected with the helper hepatitis B virus (HBV) or transduced to express the HBV envelope protein HBsAg, HLCs effectively release infectious progeny virions. We also show that HBsAg-expressing HLCs support the extracellular spread of HDV, thus providing a valuable platform for testing available anti-HDV regimens. By challenging the cells along the differentiation with HDV infection, we have identified CD63 as a potential HDV co-entry factor that was rate-limiting for HDV infection in immature hepatocytes. Given their renewable source and the potential to derive hPSCs from individual patients, we propose HLCs as a promising model for investigating HDV biology. Our findings offer new insights into HDV infection and expand the repertoire of research tools available for the development of therapeutic interventions.

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利用人体多能干细胞衍生肝细胞建立乙型和丁型肝炎病毒感染模型。

目前用于研究丁型肝炎病毒（HDV）的培养系统并不理想。在这项研究中，我们证明了从人类多能干细胞（hPSCs）中提取的类肝细胞（HLCs）对各种测试基因型的 HDV 感染具有完全的容许性。当与辅助性乙型肝炎病毒（HBV）共同感染或转导表达HBV包膜蛋白HBsAg时，HLCs能有效释放感染性原代病毒。我们还发现，表达 HBsAg 的 HLC 支持 HDV 在细胞外传播，从而为测试现有的抗 HDV 方案提供了一个宝贵的平台。通过用 HDV 感染对分化过程中的细胞进行挑战，我们发现 CD63 是一种潜在的 HDV 协同进入因子，它是 HDV 感染未成熟肝细胞的限制因素。考虑到 HLCs 的可再生来源以及从患者身上提取 hPSCs 的可能性，我们建议将 HLCs 作为研究 HDV 生物学的理想模型。我们的研究结果为了解 HDV 感染提供了新的视角，并扩大了用于开发治疗干预措施的研究工具的范围。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.