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Hepatitis C virus infection suppresses hepatitis B virus replication via the RIG-I-like helicase pathway
Mechanisms of hepatitis B virus (HBV) reactivation after hepatitis C virus (HCV) elimination by direct-acting antiviral (DAA) treatment in HBV/HCV-co-infected patients remain unclear. We examined RIG-I-like helicase (RLH) pathway activation by HBV mono-infection, HCV mono-infection or HBV/HCV co-inf...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976581/ https://www.ncbi.nlm.nih.gov/pubmed/31969598 http://dx.doi.org/10.1038/s41598-020-57603-9 |
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author | Murai, Kazuhiro Hikita, Hayato Kai, Yugo Kondo, Yasuteru Fukuoka, Makoto Fukutomi, Keisuke Doi, Akira Yamai, Takuo Nakabori, Tasuku Fukuda, Ryo Takahashi, Takeshi Miyakawa, Kei Suemizu, Hiroshi Ryo, Akihide Yamada, Ryoko Kodama, Takahiro Sakamori, Ryotaro Tatsumi, Tomohide Takehara, Tetsuo |
author_facet | Murai, Kazuhiro Hikita, Hayato Kai, Yugo Kondo, Yasuteru Fukuoka, Makoto Fukutomi, Keisuke Doi, Akira Yamai, Takuo Nakabori, Tasuku Fukuda, Ryo Takahashi, Takeshi Miyakawa, Kei Suemizu, Hiroshi Ryo, Akihide Yamada, Ryoko Kodama, Takahiro Sakamori, Ryotaro Tatsumi, Tomohide Takehara, Tetsuo |
author_sort | Murai, Kazuhiro |
collection | PubMed |
description | Mechanisms of hepatitis B virus (HBV) reactivation after hepatitis C virus (HCV) elimination by direct-acting antiviral (DAA) treatment in HBV/HCV-co-infected patients remain unclear. We examined RIG-I-like helicase (RLH) pathway activation by HBV mono-infection, HCV mono-infection or HBV/HCV co-infection and interference between HBV and HCV in primary human hepatocytes. Interference between HBV and HCV and HBV reactivation after DAA treatment in humanized-liver mice were assessed. HCV infection activated RLH pathway, as evidenced by RIG-I, ISG15 and ISG56 expression induction; HBV caused only RIG-I induction in vitro. RLH activation was also found in HBV/HCV-co-infected cells, and HBV replication were suppressed in HBV/HCV-co-infected than in HBV-mono-infected cells. siRNA-mediated double knockdown of ISG15 and ISG56 increased HBV replication in HBV/HCV-co-infected cells. HCV infection activated RLH pathway and suppressed HBV replication in humanized-liver mice. Subsequent elimination of HCV by DAA administration downregulated RLH pathway and upregulated HBV replication in mice. RLH pathway was activated in livers of chronic hepatitis C patients compared to those of chronic hepatitis B or non-B, non-C patients. The RLH pathway activation was downregulated by HCV elimination. In conclusion, HCV infection activated RLH pathway and suppressed HBV replication in human hepatocytes. HCV elimination upregulated HBV replication, probably through RLH pathway downregulation. |
format | Online Article Text |
id | pubmed-6976581 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69765812020-01-29 Hepatitis C virus infection suppresses hepatitis B virus replication via the RIG-I-like helicase pathway Murai, Kazuhiro Hikita, Hayato Kai, Yugo Kondo, Yasuteru Fukuoka, Makoto Fukutomi, Keisuke Doi, Akira Yamai, Takuo Nakabori, Tasuku Fukuda, Ryo Takahashi, Takeshi Miyakawa, Kei Suemizu, Hiroshi Ryo, Akihide Yamada, Ryoko Kodama, Takahiro Sakamori, Ryotaro Tatsumi, Tomohide Takehara, Tetsuo Sci Rep Article Mechanisms of hepatitis B virus (HBV) reactivation after hepatitis C virus (HCV) elimination by direct-acting antiviral (DAA) treatment in HBV/HCV-co-infected patients remain unclear. We examined RIG-I-like helicase (RLH) pathway activation by HBV mono-infection, HCV mono-infection or HBV/HCV co-infection and interference between HBV and HCV in primary human hepatocytes. Interference between HBV and HCV and HBV reactivation after DAA treatment in humanized-liver mice were assessed. HCV infection activated RLH pathway, as evidenced by RIG-I, ISG15 and ISG56 expression induction; HBV caused only RIG-I induction in vitro. RLH activation was also found in HBV/HCV-co-infected cells, and HBV replication were suppressed in HBV/HCV-co-infected than in HBV-mono-infected cells. siRNA-mediated double knockdown of ISG15 and ISG56 increased HBV replication in HBV/HCV-co-infected cells. HCV infection activated RLH pathway and suppressed HBV replication in humanized-liver mice. Subsequent elimination of HCV by DAA administration downregulated RLH pathway and upregulated HBV replication in mice. RLH pathway was activated in livers of chronic hepatitis C patients compared to those of chronic hepatitis B or non-B, non-C patients. The RLH pathway activation was downregulated by HCV elimination. In conclusion, HCV infection activated RLH pathway and suppressed HBV replication in human hepatocytes. HCV elimination upregulated HBV replication, probably through RLH pathway downregulation. Nature Publishing Group UK 2020-01-22 /pmc/articles/PMC6976581/ /pubmed/31969598 http://dx.doi.org/10.1038/s41598-020-57603-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Murai, Kazuhiro Hikita, Hayato Kai, Yugo Kondo, Yasuteru Fukuoka, Makoto Fukutomi, Keisuke Doi, Akira Yamai, Takuo Nakabori, Tasuku Fukuda, Ryo Takahashi, Takeshi Miyakawa, Kei Suemizu, Hiroshi Ryo, Akihide Yamada, Ryoko Kodama, Takahiro Sakamori, Ryotaro Tatsumi, Tomohide Takehara, Tetsuo Hepatitis C virus infection suppresses hepatitis B virus replication via the RIG-I-like helicase pathway |
title | Hepatitis C virus infection suppresses hepatitis B virus replication via the RIG-I-like helicase pathway |
title_full | Hepatitis C virus infection suppresses hepatitis B virus replication via the RIG-I-like helicase pathway |
title_fullStr | Hepatitis C virus infection suppresses hepatitis B virus replication via the RIG-I-like helicase pathway |
title_full_unstemmed | Hepatitis C virus infection suppresses hepatitis B virus replication via the RIG-I-like helicase pathway |
title_short | Hepatitis C virus infection suppresses hepatitis B virus replication via the RIG-I-like helicase pathway |
title_sort | hepatitis c virus infection suppresses hepatitis b virus replication via the rig-i-like helicase pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976581/ https://www.ncbi.nlm.nih.gov/pubmed/31969598 http://dx.doi.org/10.1038/s41598-020-57603-9 |
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