The hepatocyte traffic network in the human hepatitis A virus biological cycle from an evolutionary perspective
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-synten...
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| Format: | Article |
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Nature Portfolio
2025-06-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08344-w |
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| author | Albert Carcereny Alba Arrebola Gemma Chavarria-Miró Montserrat de Castellarnau Cristina Fuentes David Garcia-Pedemonte Adán Martínez-Velázquez Enric Ribes Albert Bosch Susana Guix Maria Isabel Costafreda Rosa M. Pintó |
| author_facet | Albert Carcereny Alba Arrebola Gemma Chavarria-Miró Montserrat de Castellarnau Cristina Fuentes David Garcia-Pedemonte Adán Martínez-Velázquez Enric Ribes Albert Bosch Susana Guix Maria Isabel Costafreda Rosa M. Pintó |
| author_sort | Albert Carcereny |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7c27a7ed59d24df18e053ca2cf736da3 |
| institution | DOAJ |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-7c27a7ed59d24df18e053ca2cf736da32025-08-20T03:21:06ZengNature PortfolioCommunications Biology2399-36422025-06-018111410.1038/s42003-025-08344-wThe hepatocyte traffic network in the human hepatitis A virus biological cycle from an evolutionary perspectiveAlbert Carcereny0Alba Arrebola1Gemma Chavarria-Miró2Montserrat de Castellarnau3Cristina Fuentes4David Garcia-Pedemonte5Adán Martínez-Velázquez6Enric Ribes7Albert Bosch8Susana Guix9Maria Isabel Costafreda10Rosa M. Pintó11Enteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Food Safety, University of BarcelonaEnteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Food Safety, University of BarcelonaEnteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Food Safety, University of BarcelonaEnteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Food Safety, University of BarcelonaEnteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Food Safety, University of BarcelonaEnteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Food Safety, University of BarcelonaEnteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Food Safety, University of BarcelonaEnteric Virus Laboratory, Department of Cell Biology, Physiology and Immunology, School of Biology, University of BarcelonaEnteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Food Safety, University of BarcelonaEnteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Food Safety, University of BarcelonaEnteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Food Safety, University of BarcelonaEnteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, School of Biology, and Institute of Nutrition and Food Safety, University of BarcelonaAbstract 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.https://doi.org/10.1038/s42003-025-08344-w |
| spellingShingle | Albert Carcereny Alba Arrebola Gemma Chavarria-Miró Montserrat de Castellarnau Cristina Fuentes David Garcia-Pedemonte Adán Martínez-Velázquez Enric Ribes Albert Bosch Susana Guix Maria Isabel Costafreda Rosa M. Pintó The hepatocyte traffic network in the human hepatitis A virus biological cycle from an evolutionary perspective Communications Biology |
| title | The hepatocyte traffic network in the human hepatitis A virus biological cycle from an evolutionary perspective |
| title_full | The hepatocyte traffic network in the human hepatitis A virus biological cycle from an evolutionary perspective |
| title_fullStr | The hepatocyte traffic network in the human hepatitis A virus biological cycle from an evolutionary perspective |
| title_full_unstemmed | The hepatocyte traffic network in the human hepatitis A virus biological cycle from an evolutionary perspective |
| title_short | The hepatocyte traffic network in the human hepatitis A virus biological cycle from an evolutionary perspective |
| title_sort | hepatocyte traffic network in the human hepatitis a virus biological cycle from an evolutionary perspective |
| url | https://doi.org/10.1038/s42003-025-08344-w |
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