De novo synthesis of VP16 coordinates the exit from HSV latency in vivo.

The mechanism controlling the exit from herpes simplex virus latency (HSV) is of central importance to recurrent disease and transmission of infection, yet interactions between host and viral functions that govern this process remain unclear. The cascade of HSV gene transcription is initiated by the...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Richard L Thompson, Chris M Preston, Nancy M Sawtell
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/d7ce86a1337b4473817dfc18a398f8be
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d7ce86a1337b4473817dfc18a398f8be
record_format	dspace
spelling	oai:doaj.org-article:d7ce86a1337b4473817dfc18a398f8be2021-11-25T05:47:10ZDe novo synthesis of VP16 coordinates the exit from HSV latency in vivo.1553-73661553-737410.1371/journal.ppat.1000352https://doaj.org/article/d7ce86a1337b4473817dfc18a398f8be2009-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19325890/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The mechanism controlling the exit from herpes simplex virus latency (HSV) is of central importance to recurrent disease and transmission of infection, yet interactions between host and viral functions that govern this process remain unclear. The cascade of HSV gene transcription is initiated by the multifunctional virion protein VP16, which is expressed late in the viral replication cycle. Currently, it is widely accepted that VP16 transactivating function is not involved in the exit from latency. Utilizing the mouse ocular model of HSV pathogenesis together with genetically engineered viral mutants and assays to quantify latency and the exit from latency at the single neuron level, we show that in vivo (i) the VP16 promoter confers distinct regulation critical for viral replication in the trigeminal ganglion (TG) during the acute phase of infection and (ii) the transactivation function of VP16 (VP16TF) is uniquely required for the exit from latency. TG neurons latently infected with the VP16TF mutant in1814 do not express detectable viral proteins following stress, whereas viruses with mutations in the other major viral transcription regulators ICP0 and ICP4 do exit the latent state. Analysis of a VP16 promoter/reporter mutant in the background of in1814 demonstrates that the VP16 promoter is activated in latently infected neurons following stress in the absence of other viral proteins. These findings support the novel hypothesis that de novo expression of VP16 regulates entry into the lytic program in neurons at all phases of the viral life cycle. HSV reactivation from latency conforms to a model in which stochastic derepression of the VP16 promoter and expression of VP16 initiates entry into the lytic cycle.Richard L ThompsonChris M PrestonNancy M SawtellPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 3, p e1000352 (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 Richard L Thompson Chris M Preston Nancy M Sawtell De novo synthesis of VP16 coordinates the exit from HSV latency in vivo.
description	The mechanism controlling the exit from herpes simplex virus latency (HSV) is of central importance to recurrent disease and transmission of infection, yet interactions between host and viral functions that govern this process remain unclear. The cascade of HSV gene transcription is initiated by the multifunctional virion protein VP16, which is expressed late in the viral replication cycle. Currently, it is widely accepted that VP16 transactivating function is not involved in the exit from latency. Utilizing the mouse ocular model of HSV pathogenesis together with genetically engineered viral mutants and assays to quantify latency and the exit from latency at the single neuron level, we show that in vivo (i) the VP16 promoter confers distinct regulation critical for viral replication in the trigeminal ganglion (TG) during the acute phase of infection and (ii) the transactivation function of VP16 (VP16TF) is uniquely required for the exit from latency. TG neurons latently infected with the VP16TF mutant in1814 do not express detectable viral proteins following stress, whereas viruses with mutations in the other major viral transcription regulators ICP0 and ICP4 do exit the latent state. Analysis of a VP16 promoter/reporter mutant in the background of in1814 demonstrates that the VP16 promoter is activated in latently infected neurons following stress in the absence of other viral proteins. These findings support the novel hypothesis that de novo expression of VP16 regulates entry into the lytic program in neurons at all phases of the viral life cycle. HSV reactivation from latency conforms to a model in which stochastic derepression of the VP16 promoter and expression of VP16 initiates entry into the lytic cycle.
format	article
author	Richard L Thompson Chris M Preston Nancy M Sawtell
author_facet	Richard L Thompson Chris M Preston Nancy M Sawtell
author_sort	Richard L Thompson
title	De novo synthesis of VP16 coordinates the exit from HSV latency in vivo.
title_short	De novo synthesis of VP16 coordinates the exit from HSV latency in vivo.
title_full	De novo synthesis of VP16 coordinates the exit from HSV latency in vivo.
title_fullStr	De novo synthesis of VP16 coordinates the exit from HSV latency in vivo.
title_full_unstemmed	De novo synthesis of VP16 coordinates the exit from HSV latency in vivo.
title_sort	de novo synthesis of vp16 coordinates the exit from hsv latency in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/d7ce86a1337b4473817dfc18a398f8be
work_keys_str_mv	AT richardlthompson denovosynthesisofvp16coordinatestheexitfromhsvlatencyinvivo AT chrismpreston denovosynthesisofvp16coordinatestheexitfromhsvlatencyinvivo AT nancymsawtell denovosynthesisofvp16coordinatestheexitfromhsvlatencyinvivo
_version_	1718414489129320448

De novo synthesis of VP16 coordinates the exit from HSV latency in vivo.

Ejemplares similares