The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2

Most viruses encode proteins that modulate cell-death signaling by the host. For hepatitis C virus (HCV) infection, apoptosis and other forms of cell-death have been observed in vitro and in vivo but the detailed understanding of this intricate viral-host interplay is unclear. This study examined th...

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Autores principales: Aweya, Jude Juventus, Mak, Tze Minn, Lim, Seng Gee, Tan, Yee-Joo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114515/
https://www.ncbi.nlm.nih.gov/pubmed/23246447
http://dx.doi.org/10.1016/j.virusres.2012.12.005
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author Aweya, Jude Juventus
Mak, Tze Minn
Lim, Seng Gee
Tan, Yee-Joo
author_facet Aweya, Jude Juventus
Mak, Tze Minn
Lim, Seng Gee
Tan, Yee-Joo
author_sort Aweya, Jude Juventus
collection PubMed
description Most viruses encode proteins that modulate cell-death signaling by the host. For hepatitis C virus (HCV) infection, apoptosis and other forms of cell-death have been observed in vitro and in vivo but the detailed understanding of this intricate viral-host interplay is unclear. This study examined the role played by the HCV p7 protein in the induction of cell-death. By measuring caspase-3/7 activation and cleavage of endogenous PARP, two hallmarks of apoptosis, the overexpression of p7 protein was shown to induce apoptosis in Huh7.5 cells. Furthermore, p7-induced apoptosis is caspase-dependent and involves both the intrinsic and extrinsic pathways. Similar to the M2 protein of influenza A virus, p7-induced apoptosis is independent of its ion channel activity. Coimmunoprecipitation experiments further showed that both M2 and p7 interact with the essential autophagy protein Beclin-1. However, only the M2 protein could cause an increase in the level of LC3-II, which is an indicator of autophagic activity. Thus, although the p7 protein is functionally similar to the well-characterized M2 protein, they differ in their activation of autophagic cell-death. Taken together, these results shed more light on the relationship between the HCV p7 ion channel protein and cell-death induction in host cells.
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spelling pubmed-71145152020-04-02 The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2 Aweya, Jude Juventus Mak, Tze Minn Lim, Seng Gee Tan, Yee-Joo Virus Res Article Most viruses encode proteins that modulate cell-death signaling by the host. For hepatitis C virus (HCV) infection, apoptosis and other forms of cell-death have been observed in vitro and in vivo but the detailed understanding of this intricate viral-host interplay is unclear. This study examined the role played by the HCV p7 protein in the induction of cell-death. By measuring caspase-3/7 activation and cleavage of endogenous PARP, two hallmarks of apoptosis, the overexpression of p7 protein was shown to induce apoptosis in Huh7.5 cells. Furthermore, p7-induced apoptosis is caspase-dependent and involves both the intrinsic and extrinsic pathways. Similar to the M2 protein of influenza A virus, p7-induced apoptosis is independent of its ion channel activity. Coimmunoprecipitation experiments further showed that both M2 and p7 interact with the essential autophagy protein Beclin-1. However, only the M2 protein could cause an increase in the level of LC3-II, which is an indicator of autophagic activity. Thus, although the p7 protein is functionally similar to the well-characterized M2 protein, they differ in their activation of autophagic cell-death. Taken together, these results shed more light on the relationship between the HCV p7 ion channel protein and cell-death induction in host cells. Elsevier B.V. 2013-03 2012-12-12 /pmc/articles/PMC7114515/ /pubmed/23246447 http://dx.doi.org/10.1016/j.virusres.2012.12.005 Text en Copyright © 2012 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Aweya, Jude Juventus
Mak, Tze Minn
Lim, Seng Gee
Tan, Yee-Joo
The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2
title The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2
title_full The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2
title_fullStr The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2
title_full_unstemmed The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2
title_short The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2
title_sort p7 protein of the hepatitis c virus induces cell death differently from the influenza a virus viroporin m2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114515/
https://www.ncbi.nlm.nih.gov/pubmed/23246447
http://dx.doi.org/10.1016/j.virusres.2012.12.005
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