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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...

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Autores principales: Sanada, Takahiro, Hirata, Yuichi, Naito, Yutaka, Yamamoto, Naoki, Kikkawa, Yoshiaki, Ishida, Yuji, Yamasaki, Chihiro, Tateno, Chise, Ochiya, Takahiro, Kohara, Michinori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
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.
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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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