Activation of host translational control pathways by a viral developmental switch.

In response to numerous signals, latent herpesvirus genomes abruptly switch their developmental program, aborting stable host-cell colonization in favor of productive viral replication that ultimately destroys the cell. To achieve a rapid gene expression transition, newly minted capped, polyadenylat...

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Autores principales:	Carolina Arias, Derek Walsh, Jack Harbell, Angus C Wilson, Ian Mohr
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/808210fb90214ee196e130090c3ffce2
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spelling	oai:doaj.org-article:808210fb90214ee196e130090c3ffce22021-11-25T05:47:12ZActivation of host translational control pathways by a viral developmental switch.1553-73661553-737410.1371/journal.ppat.1000334https://doaj.org/article/808210fb90214ee196e130090c3ffce22009-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19300492/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374In response to numerous signals, latent herpesvirus genomes abruptly switch their developmental program, aborting stable host-cell colonization in favor of productive viral replication that ultimately destroys the cell. To achieve a rapid gene expression transition, newly minted capped, polyadenylated viral mRNAs must engage and reprogram the cellular translational apparatus. While transcriptional responses of viral genomes undergoing lytic reactivation have been amply documented, roles for cellular translational control pathways in enabling the latent-lytic switch have not been described. Using PEL-derived B-cells naturally infected with KSHV as a model, we define efficient reactivation conditions and demonstrate that reactivation substantially changes the protein synthesis profile. New polypeptide synthesis correlates with 4E-BP1 translational repressor inactivation, nuclear PABP accumulation, eIF4F assembly, and phosphorylation of the cap-binding protein eIF4E by Mnk1. Significantly, inhibiting Mnk1 reduces accumulation of the critical viral transactivator RTA through a post-transcriptional mechanism, limiting downstream lytic protein production, and impairs reactivation efficiency. Thus, herpesvirus reactivation from latency activates the host cap-dependent translation machinery, illustrating the importance of translational regulation in implementing new developmental instructions that drastically alter cell fate.Carolina AriasDerek WalshJack HarbellAngus C WilsonIan MohrPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 3, p e1000334 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Carolina Arias Derek Walsh Jack Harbell Angus C Wilson Ian Mohr Activation of host translational control pathways by a viral developmental switch.
description	In response to numerous signals, latent herpesvirus genomes abruptly switch their developmental program, aborting stable host-cell colonization in favor of productive viral replication that ultimately destroys the cell. To achieve a rapid gene expression transition, newly minted capped, polyadenylated viral mRNAs must engage and reprogram the cellular translational apparatus. While transcriptional responses of viral genomes undergoing lytic reactivation have been amply documented, roles for cellular translational control pathways in enabling the latent-lytic switch have not been described. Using PEL-derived B-cells naturally infected with KSHV as a model, we define efficient reactivation conditions and demonstrate that reactivation substantially changes the protein synthesis profile. New polypeptide synthesis correlates with 4E-BP1 translational repressor inactivation, nuclear PABP accumulation, eIF4F assembly, and phosphorylation of the cap-binding protein eIF4E by Mnk1. Significantly, inhibiting Mnk1 reduces accumulation of the critical viral transactivator RTA through a post-transcriptional mechanism, limiting downstream lytic protein production, and impairs reactivation efficiency. Thus, herpesvirus reactivation from latency activates the host cap-dependent translation machinery, illustrating the importance of translational regulation in implementing new developmental instructions that drastically alter cell fate.
format	article
author	Carolina Arias Derek Walsh Jack Harbell Angus C Wilson Ian Mohr
author_facet	Carolina Arias Derek Walsh Jack Harbell Angus C Wilson Ian Mohr
author_sort	Carolina Arias
title	Activation of host translational control pathways by a viral developmental switch.
title_short	Activation of host translational control pathways by a viral developmental switch.
title_full	Activation of host translational control pathways by a viral developmental switch.
title_fullStr	Activation of host translational control pathways by a viral developmental switch.
title_full_unstemmed	Activation of host translational control pathways by a viral developmental switch.
title_sort	activation of host translational control pathways by a viral developmental switch.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/808210fb90214ee196e130090c3ffce2
work_keys_str_mv	AT carolinaarias activationofhosttranslationalcontrolpathwaysbyaviraldevelopmentalswitch AT derekwalsh activationofhosttranslationalcontrolpathwaysbyaviraldevelopmentalswitch AT jackharbell activationofhosttranslationalcontrolpathwaysbyaviraldevelopmentalswitch AT anguscwilson activationofhosttranslationalcontrolpathwaysbyaviraldevelopmentalswitch AT ianmohr activationofhosttranslationalcontrolpathwaysbyaviraldevelopmentalswitch
_version_	1718414465948450816

Activation of host translational control pathways by a viral developmental switch.

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