Proenca, J.T., Coleman, H.M., Nicoll, M.P., Connor, V., Preston, C.M., Arthur, J. and Efstathiou, S. (2011) An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones. Journal of General Virology, 92(11), pp. 2575-2585. (doi: 10.1099/vir.0.034728-0)
|
Text
58268.pdf Available under License Creative Commons Attribution. 712kB |
Abstract
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 Ore reporter mouse system in conjunction with Ore-expressing HSV-1 recombinants we have previously shown that activation of the IE ICPO 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 Ore 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 Ore 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.
Item Type: | Articles |
---|---|
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Preston, Prof Christopher |
Authors: | Proenca, J.T., Coleman, H.M., Nicoll, M.P., Connor, V., Preston, C.M., Arthur, J., and Efstathiou, S. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Journal of General Virology |
Journal Abbr.: | J. Gen. Virol. |
Publisher: | Society for General Microbiology |
ISSN: | 0022-1317 |
ISSN (Online): | 1465-2099 |
Copyright Holders: | Copyright © 2011 Society for General Microbiology |
First Published: | First published in Journal of General Virology 92(11):2575-2585 |
University Staff: Request a correction | Enlighten Editors: Update this record