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The host exosome pathway underpins biogenesis of the human cytomegalovirus virion

Human Cytomegalovirus (HCMV) infects over half the world's population, is a leading cause of congenital birth defects, and poses serious risks for immuno-compromised individuals. To expand the molecular knowledge governing virion maturation, we analysed HCMV virions using proteomics, and identi...

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Autores principales: Turner, Declan L, Korneev, Denis V, Purdy, John G, de Marco, Alex, Mathias, Rommel A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556872/
https://www.ncbi.nlm.nih.gov/pubmed/32910773
http://dx.doi.org/10.7554/eLife.58288
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author Turner, Declan L
Korneev, Denis V
Purdy, John G
de Marco, Alex
Mathias, Rommel A
author_facet Turner, Declan L
Korneev, Denis V
Purdy, John G
de Marco, Alex
Mathias, Rommel A
author_sort Turner, Declan L
collection PubMed
description Human Cytomegalovirus (HCMV) infects over half the world's population, is a leading cause of congenital birth defects, and poses serious risks for immuno-compromised individuals. To expand the molecular knowledge governing virion maturation, we analysed HCMV virions using proteomics, and identified a significant proportion of host exosome constituents. To validate this acquisition, we characterized exosomes released from uninfected cells, and demonstrated that over 99% of the protein cargo was subsequently incorporated into HCMV virions during infection. This suggested a common membrane origin, and utilization of host exosome machinery for virion assembly and egress. Thus, we selected a panel of exosome proteins for knock down, and confirmed that loss of 7/9 caused significantly less HCMV production. Saliently, we report that VAMP3 is essential for viral trafficking and release of infectious progeny, in various HCMV strains and cell types. Therefore, we establish that the host exosome pathway is intrinsic for HCMV maturation, and reveal new host regulators involved in viral trafficking, virion envelopment, and release. Our findings underpin future investigation of host exosome proteins as important modulators of HCMV replication with antiviral potential.
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spelling pubmed-75568722020-10-16 The host exosome pathway underpins biogenesis of the human cytomegalovirus virion Turner, Declan L Korneev, Denis V Purdy, John G de Marco, Alex Mathias, Rommel A eLife Microbiology and Infectious Disease Human Cytomegalovirus (HCMV) infects over half the world's population, is a leading cause of congenital birth defects, and poses serious risks for immuno-compromised individuals. To expand the molecular knowledge governing virion maturation, we analysed HCMV virions using proteomics, and identified a significant proportion of host exosome constituents. To validate this acquisition, we characterized exosomes released from uninfected cells, and demonstrated that over 99% of the protein cargo was subsequently incorporated into HCMV virions during infection. This suggested a common membrane origin, and utilization of host exosome machinery for virion assembly and egress. Thus, we selected a panel of exosome proteins for knock down, and confirmed that loss of 7/9 caused significantly less HCMV production. Saliently, we report that VAMP3 is essential for viral trafficking and release of infectious progeny, in various HCMV strains and cell types. Therefore, we establish that the host exosome pathway is intrinsic for HCMV maturation, and reveal new host regulators involved in viral trafficking, virion envelopment, and release. Our findings underpin future investigation of host exosome proteins as important modulators of HCMV replication with antiviral potential. eLife Sciences Publications, Ltd 2020-09-10 /pmc/articles/PMC7556872/ /pubmed/32910773 http://dx.doi.org/10.7554/eLife.58288 Text en © 2020, Turner et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Microbiology and Infectious Disease
Turner, Declan L
Korneev, Denis V
Purdy, John G
de Marco, Alex
Mathias, Rommel A
The host exosome pathway underpins biogenesis of the human cytomegalovirus virion
title The host exosome pathway underpins biogenesis of the human cytomegalovirus virion
title_full The host exosome pathway underpins biogenesis of the human cytomegalovirus virion
title_fullStr The host exosome pathway underpins biogenesis of the human cytomegalovirus virion
title_full_unstemmed The host exosome pathway underpins biogenesis of the human cytomegalovirus virion
title_short The host exosome pathway underpins biogenesis of the human cytomegalovirus virion
title_sort host exosome pathway underpins biogenesis of the human cytomegalovirus virion
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556872/
https://www.ncbi.nlm.nih.gov/pubmed/32910773
http://dx.doi.org/10.7554/eLife.58288
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