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ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction
APOBEC3G (A3G) is an innate antiviral restriction factor that strongly inhibits the replication of human immunodeficiency virus type 1 (HIV-1). An HIV-1 accessory protein, Vif, hijacks the host ubiquitin–proteasome system to execute A3G degradation. Identification of the host pathways that obstruct...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423214/ https://www.ncbi.nlm.nih.gov/pubmed/25901786 http://dx.doi.org/10.1038/ncomms7945 |
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author | Miyakawa, Kei Matsunaga, Satoko Kanou, Kazuhiko Matsuzawa, Atsushi Morishita, Ryo Kudoh, Ayumi Shindo, Keisuke Yokoyama, Masaru Sato, Hironori Kimura, Hirokazu Tamura, Tomohiko Yamamoto, Naoki Ichijo, Hidenori Takaori-Kondo, Akifumi Ryo, Akihide |
author_facet | Miyakawa, Kei Matsunaga, Satoko Kanou, Kazuhiko Matsuzawa, Atsushi Morishita, Ryo Kudoh, Ayumi Shindo, Keisuke Yokoyama, Masaru Sato, Hironori Kimura, Hirokazu Tamura, Tomohiko Yamamoto, Naoki Ichijo, Hidenori Takaori-Kondo, Akifumi Ryo, Akihide |
author_sort | Miyakawa, Kei |
collection | PubMed |
description | APOBEC3G (A3G) is an innate antiviral restriction factor that strongly inhibits the replication of human immunodeficiency virus type 1 (HIV-1). An HIV-1 accessory protein, Vif, hijacks the host ubiquitin–proteasome system to execute A3G degradation. Identification of the host pathways that obstruct the action of Vif could provide a new strategy for blocking viral replication. We demonstrate here that the host protein ASK1 (apoptosis signal-regulating kinase 1) interferes with the counteraction by Vif and revitalizes A3G-mediated viral restriction. ASK1 binds the BC-box of Vif, thereby disrupting the assembly of the Vif–ubiquitin ligase complex. Consequently, ASK1 stabilizes A3G and promotes its incorporation into viral particles, ultimately reducing viral infectivity. Furthermore, treatment with the antiretroviral drug AZT (zidovudine) induces ASK1 expression and restores the antiviral activity of A3G in HIV-1-infected cells. This study thus demonstrates a distinct function of ASK1 in restoring the host antiviral system that can be enhanced by AZT treatment. |
format | Online Article Text |
id | pubmed-4423214 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44232142015-05-20 ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction Miyakawa, Kei Matsunaga, Satoko Kanou, Kazuhiko Matsuzawa, Atsushi Morishita, Ryo Kudoh, Ayumi Shindo, Keisuke Yokoyama, Masaru Sato, Hironori Kimura, Hirokazu Tamura, Tomohiko Yamamoto, Naoki Ichijo, Hidenori Takaori-Kondo, Akifumi Ryo, Akihide Nat Commun Article APOBEC3G (A3G) is an innate antiviral restriction factor that strongly inhibits the replication of human immunodeficiency virus type 1 (HIV-1). An HIV-1 accessory protein, Vif, hijacks the host ubiquitin–proteasome system to execute A3G degradation. Identification of the host pathways that obstruct the action of Vif could provide a new strategy for blocking viral replication. We demonstrate here that the host protein ASK1 (apoptosis signal-regulating kinase 1) interferes with the counteraction by Vif and revitalizes A3G-mediated viral restriction. ASK1 binds the BC-box of Vif, thereby disrupting the assembly of the Vif–ubiquitin ligase complex. Consequently, ASK1 stabilizes A3G and promotes its incorporation into viral particles, ultimately reducing viral infectivity. Furthermore, treatment with the antiretroviral drug AZT (zidovudine) induces ASK1 expression and restores the antiviral activity of A3G in HIV-1-infected cells. This study thus demonstrates a distinct function of ASK1 in restoring the host antiviral system that can be enhanced by AZT treatment. Nature Pub. Group 2015-04-22 /pmc/articles/PMC4423214/ /pubmed/25901786 http://dx.doi.org/10.1038/ncomms7945 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Miyakawa, Kei Matsunaga, Satoko Kanou, Kazuhiko Matsuzawa, Atsushi Morishita, Ryo Kudoh, Ayumi Shindo, Keisuke Yokoyama, Masaru Sato, Hironori Kimura, Hirokazu Tamura, Tomohiko Yamamoto, Naoki Ichijo, Hidenori Takaori-Kondo, Akifumi Ryo, Akihide ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction |
title | ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction |
title_full | ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction |
title_fullStr | ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction |
title_full_unstemmed | ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction |
title_short | ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction |
title_sort | ask1 restores the antiviral activity of apobec3g by disrupting hiv-1 vif-mediated counteraction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423214/ https://www.ncbi.nlm.nih.gov/pubmed/25901786 http://dx.doi.org/10.1038/ncomms7945 |
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