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Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus
Viral control of mitochondrial quality and content has emerged as an important mechanism for counteracting the host response to virus infection. Despite the knowledge of this crucial function of some viruses, little is known about how herpesviruses regulate mitochondrial homeostasis during infection...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642096/ https://www.ncbi.nlm.nih.gov/pubmed/31324791 http://dx.doi.org/10.1038/s41467-019-11164-2 |
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author | Vo, Mai Tram Smith, Barbara J. Nicholas, John Choi, Young Bong |
author_facet | Vo, Mai Tram Smith, Barbara J. Nicholas, John Choi, Young Bong |
author_sort | Vo, Mai Tram |
collection | PubMed |
description | Viral control of mitochondrial quality and content has emerged as an important mechanism for counteracting the host response to virus infection. Despite the knowledge of this crucial function of some viruses, little is known about how herpesviruses regulate mitochondrial homeostasis during infection. Human herpesvirus 8 (HHV-8) is an oncogenic virus causally related to AIDS-associated malignancies. Here, we show that HHV-8-encoded viral interferon regulatory factor 1 (vIRF-1) promotes mitochondrial clearance by activating mitophagy to support virus replication. Genetic interference with vIRF-1 expression or targeting to the mitochondria inhibits HHV-8 replication-induced mitophagy and leads to an accumulation of mitochondria. Moreover, vIRF-1 binds directly to a mitophagy receptor, NIX, on the mitochondria and activates NIX-mediated mitophagy to promote mitochondrial clearance. Genetic and pharmacological interruption of vIRF-1/NIX-activated mitophagy inhibits HHV-8 productive replication. Our findings uncover an essential role of vIRF-1 in mitophagy activation and promotion of HHV-8 lytic replication via this mechanism. |
format | Online Article Text |
id | pubmed-6642096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66420962019-07-22 Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus Vo, Mai Tram Smith, Barbara J. Nicholas, John Choi, Young Bong Nat Commun Article Viral control of mitochondrial quality and content has emerged as an important mechanism for counteracting the host response to virus infection. Despite the knowledge of this crucial function of some viruses, little is known about how herpesviruses regulate mitochondrial homeostasis during infection. Human herpesvirus 8 (HHV-8) is an oncogenic virus causally related to AIDS-associated malignancies. Here, we show that HHV-8-encoded viral interferon regulatory factor 1 (vIRF-1) promotes mitochondrial clearance by activating mitophagy to support virus replication. Genetic interference with vIRF-1 expression or targeting to the mitochondria inhibits HHV-8 replication-induced mitophagy and leads to an accumulation of mitochondria. Moreover, vIRF-1 binds directly to a mitophagy receptor, NIX, on the mitochondria and activates NIX-mediated mitophagy to promote mitochondrial clearance. Genetic and pharmacological interruption of vIRF-1/NIX-activated mitophagy inhibits HHV-8 productive replication. Our findings uncover an essential role of vIRF-1 in mitophagy activation and promotion of HHV-8 lytic replication via this mechanism. Nature Publishing Group UK 2019-07-19 /pmc/articles/PMC6642096/ /pubmed/31324791 http://dx.doi.org/10.1038/s41467-019-11164-2 Text en © The Author(s) 2019 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 Vo, Mai Tram Smith, Barbara J. Nicholas, John Choi, Young Bong Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus |
title | Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus |
title_full | Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus |
title_fullStr | Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus |
title_full_unstemmed | Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus |
title_short | Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus |
title_sort | activation of nix-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642096/ https://www.ncbi.nlm.nih.gov/pubmed/31324791 http://dx.doi.org/10.1038/s41467-019-11164-2 |
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