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Transmission of HBV DNA Mediated by Ceramide-Triggered Extracellular Vesicles
BACKGROUND & AIMS: An extracellular vesicle (EV) is a nanovesicle that shuttles proteins, nucleic acids, and lipids, thereby influencing cell behavior. A recent crop of reports have shown that EVs are involved in infectious biology, influencing host immunity and playing a role in the viral life...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331779/ https://www.ncbi.nlm.nih.gov/pubmed/28275693 http://dx.doi.org/10.1016/j.jcmgh.2016.10.003 |
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author | Sanada, Takahiro Hirata, Yuichi Naito, Yutaka Yamamoto, Naoki Kikkawa, Yoshiaki Ishida, Yuji Yamasaki, Chihiro Tateno, Chise Ochiya, Takahiro Kohara, Michinori |
author_facet | Sanada, Takahiro Hirata, Yuichi Naito, Yutaka Yamamoto, Naoki Kikkawa, Yoshiaki Ishida, Yuji Yamasaki, Chihiro Tateno, Chise Ochiya, Takahiro Kohara, Michinori |
author_sort | Sanada, Takahiro |
collection | PubMed |
description | BACKGROUND & AIMS: An extracellular vesicle (EV) is a nanovesicle that shuttles proteins, nucleic acids, and lipids, thereby influencing cell behavior. A recent crop of reports have shown that EVs are involved in infectious biology, influencing host immunity and playing a role in the viral life cycle. In the present work, we investigated the EV-mediated transmission of hepatitis B virus (HBV) infection. METHODS: We investigated the EV-mediated transmission of HBV infection by using a HBV infectious culture system that uses primary human hepatocytes derived from humanized chimeric mice (PXB-cells). Purified EVs were isolated by ultracentrifugation. To analyze the EVs and virions, we used stimulated emission depletion microscopy. RESULTS: Purified EVs from HBV-infected PXB-cells were shown to contain HBV DNA and to be capable of transmitting HBV DNA to naive PXB-cells. These HBV-DNA–transmitting EVs were shown to be generated through a ceramide-triggered EV production pathway. Furthermore, we showed that these HBV-DNA–transmitting EVs were resistant to antibody neutralization; stimulated emission depletion microscopy showed that EVs lacked hepatitis B surface antigen, the target of neutralizing antibodies. CONCLUSIONS: These findings suggest that EVs harbor a DNA cargo capable of transmitting viral DNA into hepatocytes during HBV infection, representing an additional antibody-neutralization–resistant route of HBV infection. |
format | Online Article Text |
id | pubmed-5331779 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-53317792017-03-08 Transmission of HBV DNA Mediated by Ceramide-Triggered Extracellular Vesicles Sanada, Takahiro Hirata, Yuichi Naito, Yutaka Yamamoto, Naoki Kikkawa, Yoshiaki Ishida, Yuji Yamasaki, Chihiro Tateno, Chise Ochiya, Takahiro Kohara, Michinori Cell Mol Gastroenterol Hepatol Original Research BACKGROUND & AIMS: An extracellular vesicle (EV) is a nanovesicle that shuttles proteins, nucleic acids, and lipids, thereby influencing cell behavior. A recent crop of reports have shown that EVs are involved in infectious biology, influencing host immunity and playing a role in the viral life cycle. In the present work, we investigated the EV-mediated transmission of hepatitis B virus (HBV) infection. METHODS: We investigated the EV-mediated transmission of HBV infection by using a HBV infectious culture system that uses primary human hepatocytes derived from humanized chimeric mice (PXB-cells). Purified EVs were isolated by ultracentrifugation. To analyze the EVs and virions, we used stimulated emission depletion microscopy. RESULTS: Purified EVs from HBV-infected PXB-cells were shown to contain HBV DNA and to be capable of transmitting HBV DNA to naive PXB-cells. These HBV-DNA–transmitting EVs were shown to be generated through a ceramide-triggered EV production pathway. Furthermore, we showed that these HBV-DNA–transmitting EVs were resistant to antibody neutralization; stimulated emission depletion microscopy showed that EVs lacked hepatitis B surface antigen, the target of neutralizing antibodies. CONCLUSIONS: These findings suggest that EVs harbor a DNA cargo capable of transmitting viral DNA into hepatocytes during HBV infection, representing an additional antibody-neutralization–resistant route of HBV infection. Elsevier 2016-10-24 /pmc/articles/PMC5331779/ /pubmed/28275693 http://dx.doi.org/10.1016/j.jcmgh.2016.10.003 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Sanada, Takahiro Hirata, Yuichi Naito, Yutaka Yamamoto, Naoki Kikkawa, Yoshiaki Ishida, Yuji Yamasaki, Chihiro Tateno, Chise Ochiya, Takahiro Kohara, Michinori Transmission of HBV DNA Mediated by Ceramide-Triggered Extracellular Vesicles |
title | Transmission of HBV DNA Mediated by Ceramide-Triggered Extracellular Vesicles |
title_full | Transmission of HBV DNA Mediated by Ceramide-Triggered Extracellular Vesicles |
title_fullStr | Transmission of HBV DNA Mediated by Ceramide-Triggered Extracellular Vesicles |
title_full_unstemmed | Transmission of HBV DNA Mediated by Ceramide-Triggered Extracellular Vesicles |
title_short | Transmission of HBV DNA Mediated by Ceramide-Triggered Extracellular Vesicles |
title_sort | transmission of hbv dna mediated by ceramide-triggered extracellular vesicles |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331779/ https://www.ncbi.nlm.nih.gov/pubmed/28275693 http://dx.doi.org/10.1016/j.jcmgh.2016.10.003 |
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