从进化角度看人类甲型肝炎病毒生物周期中的肝细胞运输网络。

The hepatocyte traffic network in the human hepatitis A virus biological cycle from an evolutionary perspective.

作者信息

Carcereny Albert, Arrebola Alba, Chavarria-Miró Gemma, de Castellarnau Montserrat, Fuentes Cristina, Garcia-Pedemonte David, Martínez-Velázquez Adán, Ribes Enric, Bosch Albert, Guix Susana, Costafreda Maria Isabel, Pintó Rosa M

机构信息

Enteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Food Safety, University of Barcelona, Barcelona, Spain.

Enteric Virus Laboratory, Department of Cell Biology, Physiology and Immunology, School of Biology, University of Barcelona, Barcelona, Spain.

出版信息

Commun Biol. 2025 Jun 12;8(1):917. doi: 10.1038/s42003-025-08344-w.

DOI:10.1038/s42003-025-08344-w

PMID:40506554

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12163080/

Abstract

Hepatitis A virus (HAV) egresses from hepatocytes cloaked in exosomes (eHAV). However, the traffic network used for its release from polarized hepatocytes is not completely understood. We propose that eHAV biogenesis may follow not only an ESCRT-mediated pathway but also the syndecan-syntenin-ALIX pathway. The Bro1 and the V domains of ALIX bind to the pX extension of VP1 and the VP2-late domains of the unmature capsid, respectively. A Serine-to-Glycine replacement at position 134 of VP2, closely located with the first late domain, facilitates the interaction with ALIX promoting the syndecan-syntenin-ALIX pathway and improving the basolateral egress, preferentially using RAB35. This replacement is conserved in hepatoviruses infecting a wide range of mammalian species, but not in hepatoviruses infecting chimpanzees and humans. An inefficient basolateral egress could be a strategy to escape the antiviral cellular response in apes.

摘要

甲型肝炎病毒（HAV）以包裹在外泌体中的形式（eHAV）从肝细胞中释放出来。然而，其从极化肝细胞释放所使用的运输网络尚未完全明确。我们提出，eHAV的生物发生可能不仅遵循内体分选转运复合体（ESCRT）介导的途径，还遵循多配体聚糖- syntenin-ALIX途径。ALIX的Bro1结构域和V结构域分别与VP1的pX延伸区和未成熟衣壳的VP2晚期结构域结合。VP2第134位的丝氨酸被甘氨酸取代，该位置紧邻第一个晚期结构域，这促进了与ALIX的相互作用，推动了多配体聚糖- syntenin-ALIX途径，并优先利用RAB35改善了基底外侧的释放。这种取代在感染多种哺乳动物物种的肝病毒中是保守的，但在感染黑猩猩和人类的肝病毒中则不存在。低效的基底外侧释放可能是一种逃避猿类抗病毒细胞反应的策略。