A robust cell culture system supporting the complete life cycle of hepatitis B virus

The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as the hepatitis B virus (HBV) receptor enabled researchers to create hepatoma cell lines susceptible to HBV infection. Infection in current systems, however, is inefficient and virus fails to spread. Infection efficiency is enha...

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Main Authors: Michailidis, Eleftherios, Pabon, Jonathan, Xiang, Kuanhui, Park, Paul, Ramanan, Vyas, Hoffmann, Hans-Heinrich, Schneider, William M., de Jong, Ype P., Shlomai, Amir, Rice, Charles M., Bhatia, Sangeeta N
Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Format: Article
Published: Nature Publishing Group 2018
Online Access:http://hdl.handle.net/1721.1/118848
https://orcid.org/0000-0002-1293-2097
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author Michailidis, Eleftherios
Pabon, Jonathan
Xiang, Kuanhui
Park, Paul
Ramanan, Vyas
Hoffmann, Hans-Heinrich
Schneider, William M.
de Jong, Ype P.
Shlomai, Amir
Rice, Charles M.
Bhatia, Sangeeta N
author2 Massachusetts Institute of Technology. Institute for Medical Engineering & Science
author_facet Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Michailidis, Eleftherios
Pabon, Jonathan
Xiang, Kuanhui
Park, Paul
Ramanan, Vyas
Hoffmann, Hans-Heinrich
Schneider, William M.
de Jong, Ype P.
Shlomai, Amir
Rice, Charles M.
Bhatia, Sangeeta N
author_sort Michailidis, Eleftherios
collection MIT
description The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as the hepatitis B virus (HBV) receptor enabled researchers to create hepatoma cell lines susceptible to HBV infection. Infection in current systems, however, is inefficient and virus fails to spread. Infection efficiency is enhanced by treating cells with polyethylene glycol 8000 (PEG) during infection. However, this alone does not promote virus spread. Here we show that maintaining PEG in culture medium increases the rate of infection by at least one order of magnitude, and, most importantly, promotes virus spread. To demonstrate the utility of this system, we show that two interferon-stimulated genes (ISGs), ISG20 and tetherin, restrict HBV spread in NTCP-expressing hepatoma cells. Thus, this protocol can be easily applied to existing cell culture systems to study the complete HBV life cycle, including virus spread.
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spelling mit-1721.1/1188482022-09-23T10:31:43Z A robust cell culture system supporting the complete life cycle of hepatitis B virus Michailidis, Eleftherios Pabon, Jonathan Xiang, Kuanhui Park, Paul Ramanan, Vyas Hoffmann, Hans-Heinrich Schneider, William M. de Jong, Ype P. Shlomai, Amir Rice, Charles M. Bhatia, Sangeeta N Massachusetts Institute of Technology. Institute for Medical Engineering & Science Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Koch Institute for Integrative Cancer Research at MIT Bhatia, Sangeeta N The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as the hepatitis B virus (HBV) receptor enabled researchers to create hepatoma cell lines susceptible to HBV infection. Infection in current systems, however, is inefficient and virus fails to spread. Infection efficiency is enhanced by treating cells with polyethylene glycol 8000 (PEG) during infection. However, this alone does not promote virus spread. Here we show that maintaining PEG in culture medium increases the rate of infection by at least one order of magnitude, and, most importantly, promotes virus spread. To demonstrate the utility of this system, we show that two interferon-stimulated genes (ISGs), ISG20 and tetherin, restrict HBV spread in NTCP-expressing hepatoma cells. Thus, this protocol can be easily applied to existing cell culture systems to study the complete HBV life cycle, including virus spread. 2018-11-02T18:34:22Z 2018-11-02T18:34:22Z 2017-11 2017-10 2018-10-11T16:13:41Z Article http://purl.org/eprint/type/JournalArticle 2045-2322 http://hdl.handle.net/1721.1/118848 Michailidis, Eleftherios et al. “A Robust Cell Culture System Supporting the Complete Life Cycle of Hepatitis B Virus.” Scientific Reports 7, 1 (November 2017): 16616 © 2017 The Author(s) https://orcid.org/0000-0002-1293-2097 http://dx.doi.org/10.1038/S41598-017-16882-5 Scientific Reports Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature
spellingShingle Michailidis, Eleftherios
Pabon, Jonathan
Xiang, Kuanhui
Park, Paul
Ramanan, Vyas
Hoffmann, Hans-Heinrich
Schneider, William M.
de Jong, Ype P.
Shlomai, Amir
Rice, Charles M.
Bhatia, Sangeeta N
A robust cell culture system supporting the complete life cycle of hepatitis B virus
title A robust cell culture system supporting the complete life cycle of hepatitis B virus
title_full A robust cell culture system supporting the complete life cycle of hepatitis B virus
title_fullStr A robust cell culture system supporting the complete life cycle of hepatitis B virus
title_full_unstemmed A robust cell culture system supporting the complete life cycle of hepatitis B virus
title_short A robust cell culture system supporting the complete life cycle of hepatitis B virus
title_sort robust cell culture system supporting the complete life cycle of hepatitis b virus
url http://hdl.handle.net/1721.1/118848
https://orcid.org/0000-0002-1293-2097
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