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Host Protein BAG3 is a Negative Regulator of Lassa VLP Egress
Lassa fever virus (LFV) belongs to the Arenaviridae family and can cause acute hemorrhagic fever in humans. The LFV Z protein plays a central role in virion assembly and egress, such that independent expression of LFV Z leads to the production of virus-like particles (VLPs) that mimic egress of infe...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163595/ https://www.ncbi.nlm.nih.gov/pubmed/30011814 http://dx.doi.org/10.3390/diseases6030064 |
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author | Han, Ziying Schwoerer, Michael P. Hicks, Philip Liang, Jingjing Ruthel, Gordon Berry, Corbett T. Freedman, Bruce D. Sagum, Cari A. Bedford, Mark T. Sidhu, Sachdev S. Sudol, Marius Harty, Ronald N. |
author_facet | Han, Ziying Schwoerer, Michael P. Hicks, Philip Liang, Jingjing Ruthel, Gordon Berry, Corbett T. Freedman, Bruce D. Sagum, Cari A. Bedford, Mark T. Sidhu, Sachdev S. Sudol, Marius Harty, Ronald N. |
author_sort | Han, Ziying |
collection | PubMed |
description | Lassa fever virus (LFV) belongs to the Arenaviridae family and can cause acute hemorrhagic fever in humans. The LFV Z protein plays a central role in virion assembly and egress, such that independent expression of LFV Z leads to the production of virus-like particles (VLPs) that mimic egress of infectious virus. LFV Z contains both PTAP and PPPY L-domain motifs that are known to recruit host proteins that are important for mediating efficient virus egress and spread. The viral PPPY motif is known to interact with specific host WW-domain bearing proteins. Here we identified host WW-domain bearing protein BCL2 Associated Athanogene 3 (BAG3) as a LFV Z PPPY interactor using our proline-rich reading array of WW-domain containing mammalian proteins. BAG3 is a stress-induced molecular co-chaperone that functions to regulate cellular protein homeostasis and cell survival via Chaperone-Assisted Selective Autophagy (CASA). Similar to our previously published findings for the VP40 proteins of Ebola and Marburg viruses, our results using VLP budding assays, BAG3 knockout cells, and confocal microscopy indicate that BAG3 is a WW-domain interactor that negatively regulates egress of LFV Z VLPs, rather than promoting VLP release. Our results suggest that CASA and specifically BAG3 may represent a novel host defense mechanism, whereby BAG3 may dampen egress of several hemorrhagic fever viruses by interacting and interfering with the budding function of viral PPxY-containing matrix proteins. |
format | Online Article Text |
id | pubmed-6163595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61635952018-10-11 Host Protein BAG3 is a Negative Regulator of Lassa VLP Egress Han, Ziying Schwoerer, Michael P. Hicks, Philip Liang, Jingjing Ruthel, Gordon Berry, Corbett T. Freedman, Bruce D. Sagum, Cari A. Bedford, Mark T. Sidhu, Sachdev S. Sudol, Marius Harty, Ronald N. Diseases Article Lassa fever virus (LFV) belongs to the Arenaviridae family and can cause acute hemorrhagic fever in humans. The LFV Z protein plays a central role in virion assembly and egress, such that independent expression of LFV Z leads to the production of virus-like particles (VLPs) that mimic egress of infectious virus. LFV Z contains both PTAP and PPPY L-domain motifs that are known to recruit host proteins that are important for mediating efficient virus egress and spread. The viral PPPY motif is known to interact with specific host WW-domain bearing proteins. Here we identified host WW-domain bearing protein BCL2 Associated Athanogene 3 (BAG3) as a LFV Z PPPY interactor using our proline-rich reading array of WW-domain containing mammalian proteins. BAG3 is a stress-induced molecular co-chaperone that functions to regulate cellular protein homeostasis and cell survival via Chaperone-Assisted Selective Autophagy (CASA). Similar to our previously published findings for the VP40 proteins of Ebola and Marburg viruses, our results using VLP budding assays, BAG3 knockout cells, and confocal microscopy indicate that BAG3 is a WW-domain interactor that negatively regulates egress of LFV Z VLPs, rather than promoting VLP release. Our results suggest that CASA and specifically BAG3 may represent a novel host defense mechanism, whereby BAG3 may dampen egress of several hemorrhagic fever viruses by interacting and interfering with the budding function of viral PPxY-containing matrix proteins. MDPI 2018-07-13 /pmc/articles/PMC6163595/ /pubmed/30011814 http://dx.doi.org/10.3390/diseases6030064 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Han, Ziying Schwoerer, Michael P. Hicks, Philip Liang, Jingjing Ruthel, Gordon Berry, Corbett T. Freedman, Bruce D. Sagum, Cari A. Bedford, Mark T. Sidhu, Sachdev S. Sudol, Marius Harty, Ronald N. Host Protein BAG3 is a Negative Regulator of Lassa VLP Egress |
title | Host Protein BAG3 is a Negative Regulator of Lassa VLP Egress |
title_full | Host Protein BAG3 is a Negative Regulator of Lassa VLP Egress |
title_fullStr | Host Protein BAG3 is a Negative Regulator of Lassa VLP Egress |
title_full_unstemmed | Host Protein BAG3 is a Negative Regulator of Lassa VLP Egress |
title_short | Host Protein BAG3 is a Negative Regulator of Lassa VLP Egress |
title_sort | host protein bag3 is a negative regulator of lassa vlp egress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163595/ https://www.ncbi.nlm.nih.gov/pubmed/30011814 http://dx.doi.org/10.3390/diseases6030064 |
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