Nipah Virus-Like Particle Egress Is Modulated by Cytoskeletal and Vesicular Trafficking Pathways: a Validated Particle Proteomics Analysis

ABSTRACT Classified as a biosafety level 4 (BSL4) select agent, Nipah virus (NiV) is a deadly henipavirus in the Paramyxoviridae family, with a nearly 75% mortality rate in humans, underscoring its global and animal health importance. Elucidating the process of viral particle production in host cell...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Gunner P. Johnston, Birgit Bradel-Tretheway, Paul D. Piehowski, Heather M. Brewer, Bom Nae Rin Lee, Nicholas T. Usher, J. Lizbeth Reyes Zamora, Victoria Ortega, Erik M. Contreras, Jeremy R. Teuton, Jason P. Wendler, Keesha M. Matz, Joshua N. Adkins, Hector C. Aguilar
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Nipah virus paramyxovirus proteomics vesicular trafficking endocytosis cytoskeleton Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/06fb4e8b326948b780ec64ff4fbf9a2f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:06fb4e8b326948b780ec64ff4fbf9a2f
record_format	dspace
spelling	oai:doaj.org-article:06fb4e8b326948b780ec64ff4fbf9a2f2021-12-02T18:39:16ZNipah Virus-Like Particle Egress Is Modulated by Cytoskeletal and Vesicular Trafficking Pathways: a Validated Particle Proteomics Analysis10.1128/mSystems.00194-192379-5077https://doaj.org/article/06fb4e8b326948b780ec64ff4fbf9a2f2019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00194-19https://doaj.org/toc/2379-5077ABSTRACT Classified as a biosafety level 4 (BSL4) select agent, Nipah virus (NiV) is a deadly henipavirus in the Paramyxoviridae family, with a nearly 75% mortality rate in humans, underscoring its global and animal health importance. Elucidating the process of viral particle production in host cells is imperative both for targeted drug design and viral particle-based vaccine development. However, little is understood concerning the functions of cellular machinery in paramyxoviral and henipaviral assembly and budding. Recent studies showed evidence for the involvement of multiple NiV proteins in viral particle formation, in contrast to the mechanisms understood for several paramyxoviruses as being reliant on the matrix (M) protein alone. Further, the levels and purposes of cellular factor incorporation into viral particles are largely unexplored for the paramyxoviruses. To better understand the involvement of cellular machinery and the major structural viral fusion (F), attachment (G), and matrix (M) proteins, we performed proteomics analyses on virus-like particles (VLPs) produced from several combinations of these NiV proteins. Our findings indicate that NiV VLPs incorporate vesicular trafficking and actin cytoskeletal factors. The involvement of these biological processes was validated by experiments indicating that the perturbation of key factors in these cellular processes substantially modulated viral particle formation. These effects were most impacted for NiV-F-modulated viral particle formation either autonomously or in combination with other NiV proteins, indicating that NiV-F budding relies heavily on these cellular processes. These findings indicate a significant involvement of the NiV fusion protein, vesicular trafficking, and actin cytoskeletal processes in efficient viral particle formation. IMPORTANCE Nipah virus is a zoonotic biosafety level 4 agent with high mortality rates in humans. The genus to which Nipah virus belongs, Henipavirus, includes five officially recognized pathogens; however, over 20 species have been identified in multiple continents within the last several years. As there are still no vaccines or treatments for NiV infection, elucidating its process of viral particle production is imperative both for targeted drug design as well as for particle-based vaccine development. Developments in high-throughput technologies make proteomic analysis of isolated viral particles a highly insightful approach to understanding the life cycle of pathogens such as Nipah virus.Gunner P. JohnstonBirgit Bradel-TrethewayPaul D. PiehowskiHeather M. BrewerBom Nae Rin LeeNicholas T. UsherJ. Lizbeth Reyes ZamoraVictoria OrtegaErik M. ContrerasJeremy R. TeutonJason P. WendlerKeesha M. MatzJoshua N. AdkinsHector C. AguilarAmerican Society for MicrobiologyarticleNipah virusparamyxovirusproteomicsvesicular traffickingendocytosiscytoskeletonMicrobiologyQR1-502ENmSystems, Vol 4, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nipah virus paramyxovirus proteomics vesicular trafficking endocytosis cytoskeleton Microbiology QR1-502
spellingShingle	Nipah virus paramyxovirus proteomics vesicular trafficking endocytosis cytoskeleton Microbiology QR1-502 Gunner P. Johnston Birgit Bradel-Tretheway Paul D. Piehowski Heather M. Brewer Bom Nae Rin Lee Nicholas T. Usher J. Lizbeth Reyes Zamora Victoria Ortega Erik M. Contreras Jeremy R. Teuton Jason P. Wendler Keesha M. Matz Joshua N. Adkins Hector C. Aguilar Nipah Virus-Like Particle Egress Is Modulated by Cytoskeletal and Vesicular Trafficking Pathways: a Validated Particle Proteomics Analysis
description	ABSTRACT Classified as a biosafety level 4 (BSL4) select agent, Nipah virus (NiV) is a deadly henipavirus in the Paramyxoviridae family, with a nearly 75% mortality rate in humans, underscoring its global and animal health importance. Elucidating the process of viral particle production in host cells is imperative both for targeted drug design and viral particle-based vaccine development. However, little is understood concerning the functions of cellular machinery in paramyxoviral and henipaviral assembly and budding. Recent studies showed evidence for the involvement of multiple NiV proteins in viral particle formation, in contrast to the mechanisms understood for several paramyxoviruses as being reliant on the matrix (M) protein alone. Further, the levels and purposes of cellular factor incorporation into viral particles are largely unexplored for the paramyxoviruses. To better understand the involvement of cellular machinery and the major structural viral fusion (F), attachment (G), and matrix (M) proteins, we performed proteomics analyses on virus-like particles (VLPs) produced from several combinations of these NiV proteins. Our findings indicate that NiV VLPs incorporate vesicular trafficking and actin cytoskeletal factors. The involvement of these biological processes was validated by experiments indicating that the perturbation of key factors in these cellular processes substantially modulated viral particle formation. These effects were most impacted for NiV-F-modulated viral particle formation either autonomously or in combination with other NiV proteins, indicating that NiV-F budding relies heavily on these cellular processes. These findings indicate a significant involvement of the NiV fusion protein, vesicular trafficking, and actin cytoskeletal processes in efficient viral particle formation. IMPORTANCE Nipah virus is a zoonotic biosafety level 4 agent with high mortality rates in humans. The genus to which Nipah virus belongs, Henipavirus, includes five officially recognized pathogens; however, over 20 species have been identified in multiple continents within the last several years. As there are still no vaccines or treatments for NiV infection, elucidating its process of viral particle production is imperative both for targeted drug design as well as for particle-based vaccine development. Developments in high-throughput technologies make proteomic analysis of isolated viral particles a highly insightful approach to understanding the life cycle of pathogens such as Nipah virus.
format	article
author	Gunner P. Johnston Birgit Bradel-Tretheway Paul D. Piehowski Heather M. Brewer Bom Nae Rin Lee Nicholas T. Usher J. Lizbeth Reyes Zamora Victoria Ortega Erik M. Contreras Jeremy R. Teuton Jason P. Wendler Keesha M. Matz Joshua N. Adkins Hector C. Aguilar
author_facet	Gunner P. Johnston Birgit Bradel-Tretheway Paul D. Piehowski Heather M. Brewer Bom Nae Rin Lee Nicholas T. Usher J. Lizbeth Reyes Zamora Victoria Ortega Erik M. Contreras Jeremy R. Teuton Jason P. Wendler Keesha M. Matz Joshua N. Adkins Hector C. Aguilar
author_sort	Gunner P. Johnston
title	Nipah Virus-Like Particle Egress Is Modulated by Cytoskeletal and Vesicular Trafficking Pathways: a Validated Particle Proteomics Analysis
title_short	Nipah Virus-Like Particle Egress Is Modulated by Cytoskeletal and Vesicular Trafficking Pathways: a Validated Particle Proteomics Analysis
title_full	Nipah Virus-Like Particle Egress Is Modulated by Cytoskeletal and Vesicular Trafficking Pathways: a Validated Particle Proteomics Analysis
title_fullStr	Nipah Virus-Like Particle Egress Is Modulated by Cytoskeletal and Vesicular Trafficking Pathways: a Validated Particle Proteomics Analysis
title_full_unstemmed	Nipah Virus-Like Particle Egress Is Modulated by Cytoskeletal and Vesicular Trafficking Pathways: a Validated Particle Proteomics Analysis
title_sort	nipah virus-like particle egress is modulated by cytoskeletal and vesicular trafficking pathways: a validated particle proteomics analysis
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/06fb4e8b326948b780ec64ff4fbf9a2f
work_keys_str_mv	AT gunnerpjohnston nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis AT birgitbradeltretheway nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis AT pauldpiehowski nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis AT heathermbrewer nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis AT bomnaerinlee nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis AT nicholastusher nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis AT jlizbethreyeszamora nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis AT victoriaortega nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis AT erikmcontreras nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis AT jeremyrteuton nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis AT jasonpwendler nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis AT keeshammatz nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis AT joshuanadkins nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis AT hectorcaguilar nipahviruslikeparticleegressismodulatedbycytoskeletalandvesiculartraffickingpathwaysavalidatedparticleproteomicsanalysis
_version_	1718377720748965888

Nipah Virus-Like Particle Egress Is Modulated by Cytoskeletal and Vesicular Trafficking Pathways: a Validated Particle Proteomics Analysis

Ejemplares similares