INRS-Centre Armand-Frappier Santé Biotechnologie, Laval, QC H7V 1B7, Canada.
Viruses. 2024 May 22;16(6):825. doi: 10.3390/v16060825.
A number of research studies, including ours, have spotlighted exosomes as critical facilitators of viral dissemination. While hepatitis B virus (HBV) transmission through exosomes has been studied, the focus on its satellite virus, the hepatitis delta virus (HDV), has been unexplored in this context. HDV, although being a defective virus, can replicate its genome autonomously within hepatocytes, independently of HBV. Investigations on Huh7 cells revealed an intriguing phenomenon: the HDV proteins, S-HDAg and L-HDAg, are transmitted between cells without a complete viral structure. Detailed analysis further revealed that the expression of these proteins not only bolstered exosome secretion but also ensured their enrichment within these vesicles. Our experimental approach utilized transfection of various plasmids to examine the role of HDV RNA and proteins in the process. One salient finding was the differential propagation of the HDV proteins S-HDAg and L-HDAg, suggesting intricate molecular mechanisms behind their transmission. Notably, the purity of our exosome preparations was monitored using markers such as TSG101 and CD81. Importantly, these exosomes were found to carry both HDV RNA and proteins, highlighting their role in HDV dissemination. This novel study underscores the role of exosomes in mediating the transmission of HDV components between hepatocytes independent of HBV. These revelations about the exosomal pathway of HDV transmission provide a foundation for the development of innovative therapeutic strategies against HDV infections.
许多研究,包括我们的研究,都强调了外泌体作为病毒传播的关键促进因素。虽然已经研究了乙型肝炎病毒(HBV)通过外泌体的传播,但在这种情况下,其卫星病毒——丁型肝炎病毒(HDV)尚未得到探索。尽管 HDV 是一种缺陷病毒,但它可以在肝细胞内自主复制其基因组,而不依赖于 HBV。对 Huh7 细胞的研究揭示了一个有趣的现象:HDV 蛋白 S-HDAg 和 L-HDAg 在没有完整病毒结构的情况下在细胞间传递。进一步的详细分析表明,这些蛋白的表达不仅增强了外泌体的分泌,而且确保了它们在这些囊泡中的富集。我们的实验方法利用转染各种质粒来研究 HDV RNA 和蛋白在该过程中的作用。一个显著的发现是 HDV 蛋白 S-HDAg 和 L-HDAg 的差异传播,表明它们在传播过程中存在复杂的分子机制。值得注意的是,我们使用 TSG101 和 CD81 等标志物来监测外泌体制剂的纯度。重要的是,这些外泌体携带 HDV RNA 和蛋白,突出了它们在 HDV 传播中的作用。这项新的研究强调了外泌体在介导 HDV 成分在肝细胞间传播中的作用,而不依赖于 HBV。这些关于 HDV 外泌体传播途径的发现为针对 HDV 感染的创新治疗策略的发展提供了基础。