Transient reversal of episome silencing precedes VP16-dependent transcription during reactivation of latent HSV-1 in neurons.
Herpes simplex virus type-1 (HSV-1) establishes latency in peripheral neurons, creating a permanent source of recurrent infections. The latent genome is assembled into chromatin and lytic cycle genes are silenced. Processes that orchestrate reentry into productive replication (reactivation) remain p...
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2012-02-01
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Series: | PLoS Pathogens |
Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22383875/pdf/?tool=EBI |
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doaj-a581ea214a5f49e8888b2120c99472652021-04-21T17:29:00ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-02-0182e100254010.1371/journal.ppat.1002540Transient reversal of episome silencing precedes VP16-dependent transcription during reactivation of latent HSV-1 in neurons.Ju Youn KimAngelo MandarinoMoses V ChaoIan MohrAngus C WilsonHerpes simplex virus type-1 (HSV-1) establishes latency in peripheral neurons, creating a permanent source of recurrent infections. The latent genome is assembled into chromatin and lytic cycle genes are silenced. Processes that orchestrate reentry into productive replication (reactivation) remain poorly understood. We have used latently infected cultures of primary superior cervical ganglion (SCG) sympathetic neurons to profile viral gene expression following a defined reactivation stimulus. Lytic genes are transcribed in two distinct phases, differing in their reliance on protein synthesis, viral DNA replication and the essential initiator protein VP16. The first phase does not require viral proteins and has the appearance of a transient, widespread de-repression of the previously silent lytic genes. This allows synthesis of viral regulatory proteins including VP16, which accumulate in the cytoplasm of the host neuron. During the second phase, VP16 and its cellular cofactor HCF-1, which is also predominantly cytoplasmic, concentrate in the nucleus where they assemble an activator complex on viral promoters. The transactivation function supplied by VP16 promotes increased viral lytic gene transcription leading to the onset of genome amplification and the production of infectious viral particles. Thus regulated localization of de novo synthesized VP16 is likely to be a critical determinant of HSV-1 reactivation in sympathetic neurons.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22383875/pdf/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ju Youn Kim Angelo Mandarino Moses V Chao Ian Mohr Angus C Wilson |
spellingShingle |
Ju Youn Kim Angelo Mandarino Moses V Chao Ian Mohr Angus C Wilson Transient reversal of episome silencing precedes VP16-dependent transcription during reactivation of latent HSV-1 in neurons. PLoS Pathogens |
author_facet |
Ju Youn Kim Angelo Mandarino Moses V Chao Ian Mohr Angus C Wilson |
author_sort |
Ju Youn Kim |
title |
Transient reversal of episome silencing precedes VP16-dependent transcription during reactivation of latent HSV-1 in neurons. |
title_short |
Transient reversal of episome silencing precedes VP16-dependent transcription during reactivation of latent HSV-1 in neurons. |
title_full |
Transient reversal of episome silencing precedes VP16-dependent transcription during reactivation of latent HSV-1 in neurons. |
title_fullStr |
Transient reversal of episome silencing precedes VP16-dependent transcription during reactivation of latent HSV-1 in neurons. |
title_full_unstemmed |
Transient reversal of episome silencing precedes VP16-dependent transcription during reactivation of latent HSV-1 in neurons. |
title_sort |
transient reversal of episome silencing precedes vp16-dependent transcription during reactivation of latent hsv-1 in neurons. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2012-02-01 |
description |
Herpes simplex virus type-1 (HSV-1) establishes latency in peripheral neurons, creating a permanent source of recurrent infections. The latent genome is assembled into chromatin and lytic cycle genes are silenced. Processes that orchestrate reentry into productive replication (reactivation) remain poorly understood. We have used latently infected cultures of primary superior cervical ganglion (SCG) sympathetic neurons to profile viral gene expression following a defined reactivation stimulus. Lytic genes are transcribed in two distinct phases, differing in their reliance on protein synthesis, viral DNA replication and the essential initiator protein VP16. The first phase does not require viral proteins and has the appearance of a transient, widespread de-repression of the previously silent lytic genes. This allows synthesis of viral regulatory proteins including VP16, which accumulate in the cytoplasm of the host neuron. During the second phase, VP16 and its cellular cofactor HCF-1, which is also predominantly cytoplasmic, concentrate in the nucleus where they assemble an activator complex on viral promoters. The transactivation function supplied by VP16 promotes increased viral lytic gene transcription leading to the onset of genome amplification and the production of infectious viral particles. Thus regulated localization of de novo synthesized VP16 is likely to be a critical determinant of HSV-1 reactivation in sympathetic neurons. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22383875/pdf/?tool=EBI |
work_keys_str_mv |
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