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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doaj-a071ccccecbd48ac9eef34aa58b408e52021-05-05T21:30:05ZengeLife Sciences Publications LtdeLife2050-084X2020-09-01910.7554/eLife.58288The host exosome pathway underpins biogenesis of the human cytomegalovirus virionDeclan L Turner0https://orcid.org/0000-0002-7643-2796Denis V Korneev1https://orcid.org/0000-0003-4350-8317John G Purdy2https://orcid.org/0000-0001-7460-7567Alex de Marco3https://orcid.org/0000-0001-6238-5653Rommel A Mathias4https://orcid.org/0000-0003-3064-4897Infection and Immunity Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Victoria, AustraliaSchool of Biological Sciences, Monash University, Victoria, AustraliaDepartment of Immunobiology and BIO5 Institute, University of Arizona, Tucson, United StatesInfection and Immunity Program, Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Victoria, Australia; University of Warwick, Coventry, United KingdomInfection and Immunity Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Victoria, Australia; Infection and Immunity Program, Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Victoria, AustraliaHuman 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.https://elifesciences.org/articles/58288HCMVexosomeproteomicsvirion assemblyegressherpesvirus |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Declan L Turner Denis V Korneev John G Purdy Alex de Marco Rommel A Mathias |
spellingShingle |
Declan L Turner Denis V Korneev John G Purdy Alex de Marco Rommel A Mathias The host exosome pathway underpins biogenesis of the human cytomegalovirus virion eLife HCMV exosome proteomics virion assembly egress herpesvirus |
author_facet |
Declan L Turner Denis V Korneev John G Purdy Alex de Marco Rommel A Mathias |
author_sort |
Declan L Turner |
title |
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_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_sort |
host exosome pathway underpins biogenesis of the human cytomegalovirus virion |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2020-09-01 |
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. |
topic |
HCMV exosome proteomics virion assembly egress herpesvirus |
url |
https://elifesciences.org/articles/58288 |
work_keys_str_mv |
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