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An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones
Herpes simplex virus (HSV) type-1 establishes lifelong latency in sensory neurones and it is widely assumed that latency is the consequence of a failure to initiate virus immediate-early (IE) gene expression. However, using a Cre reporter mouse system in conjunction with Cre-expressing HSV-1 recombi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Society for General Microbiology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541806/ https://www.ncbi.nlm.nih.gov/pubmed/21752961 http://dx.doi.org/10.1099/vir.0.034728-0 |
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author | Proença, João T. Coleman, Heather M. Nicoll, Michael P. Connor, Viv Preston, Christopher M. Arthur, Jane Efstathiou, Stacey |
author_facet | Proença, João T. Coleman, Heather M. Nicoll, Michael P. Connor, Viv Preston, Christopher M. Arthur, Jane Efstathiou, Stacey |
author_sort | Proença, João T. |
collection | PubMed |
description | Herpes simplex virus (HSV) type-1 establishes lifelong latency in sensory neurones and it is widely assumed that latency is the consequence of a failure to initiate virus immediate-early (IE) gene expression. However, using a Cre reporter mouse system in conjunction with Cre-expressing HSV-1 recombinants we have previously shown that activation of the IE ICP0 promoter can precede latency establishment in at least 30 % of latently infected cells. During productive infection of non-neuronal cells, IE promoter activation is largely dependent on the transactivator VP16 a late structural component of the virion. Of significance, VP16 has recently been shown to exhibit altered regulation in neurones; where its de novo synthesis is necessary for IE gene expression during both lytic infection and reactivation from latency. In the current study, we utilized the Cre reporter mouse model system to characterize the full extent of viral promoter activity compatible with cell survival and latency establishment. In contrast to the high frequency activation of representative IE promoters prior to latency establishment, cell marking using a virus recombinant expressing Cre under VP16 promoter control was very inefficient. Furthermore, infection of neuronal cultures with VP16 mutants reveals a strong VP16 requirement for IE promoter activity in non-neuronal cells, but not sensory neurones. We conclude that only IE promoter activation can efficiently precede latency establishment and that this activation is likely to occur through a VP16-independent mechanism. |
format | Online Article Text |
id | pubmed-3541806 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Society for General Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-35418062013-04-24 An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones Proença, João T. Coleman, Heather M. Nicoll, Michael P. Connor, Viv Preston, Christopher M. Arthur, Jane Efstathiou, Stacey J Gen Virol Animal Herpes simplex virus (HSV) type-1 establishes lifelong latency in sensory neurones and it is widely assumed that latency is the consequence of a failure to initiate virus immediate-early (IE) gene expression. However, using a Cre reporter mouse system in conjunction with Cre-expressing HSV-1 recombinants we have previously shown that activation of the IE ICP0 promoter can precede latency establishment in at least 30 % of latently infected cells. During productive infection of non-neuronal cells, IE promoter activation is largely dependent on the transactivator VP16 a late structural component of the virion. Of significance, VP16 has recently been shown to exhibit altered regulation in neurones; where its de novo synthesis is necessary for IE gene expression during both lytic infection and reactivation from latency. In the current study, we utilized the Cre reporter mouse model system to characterize the full extent of viral promoter activity compatible with cell survival and latency establishment. In contrast to the high frequency activation of representative IE promoters prior to latency establishment, cell marking using a virus recombinant expressing Cre under VP16 promoter control was very inefficient. Furthermore, infection of neuronal cultures with VP16 mutants reveals a strong VP16 requirement for IE promoter activity in non-neuronal cells, but not sensory neurones. We conclude that only IE promoter activation can efficiently precede latency establishment and that this activation is likely to occur through a VP16-independent mechanism. Society for General Microbiology 2011-11 /pmc/articles/PMC3541806/ /pubmed/21752961 http://dx.doi.org/10.1099/vir.0.034728-0 Text en © 2011 SGM http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Animal Proença, João T. Coleman, Heather M. Nicoll, Michael P. Connor, Viv Preston, Christopher M. Arthur, Jane Efstathiou, Stacey An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones |
title | An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones |
title_full | An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones |
title_fullStr | An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones |
title_full_unstemmed | An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones |
title_short | An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones |
title_sort | investigation of herpes simplex virus promoter activity compatible with latency establishment reveals vp16-independent activation of immediate-early promoters in sensory neurones |
topic | Animal |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541806/ https://www.ncbi.nlm.nih.gov/pubmed/21752961 http://dx.doi.org/10.1099/vir.0.034728-0 |
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