Wright, Jordan and Leppard, Keith (2013) The human adenovirus 5 L4 promoter is activated by cellular stress response protein p53. Journal of Virology, Volume 87 (Number 21). pp. 11617-11625. doi:10.1128/JVI.01924-13 ISSN 0022-538X.

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Abstract

During adenovirus infection, the emphasis of gene expression switches from early genes to late genes in a highly regulated manner. Two gene products, L4-22K and L4-33K, contribute to this switch by activating the Major Late Transcription Unit (MLTU) and regulating the splicing of its transcript. L4-22K and L4-33K expression is driven initially by a recently described L4 promoter (L4P) embedded within the MLTU that is activated by early and intermediate viral factors: E1A, E4 Orf3 and IVa2. Here we show that this promoter is also significantly activated by the cellular stress response regulator, p53. Exogenous expression of p53 activated L4P in reporter assays whilst depletion of endogenous p53 inhibited the induction of L4P by viral activators. Chromatin immunoprecipitation studies showed that p53 associates with L4P and that during adenovirus type 5 (Ad5) infection this association peaks at 12 h.p.i., coinciding with the phase of the infectious cycle when L4P is active, and is then lost as MLP activation commences. P53 activation of L4P is significant during Ad5 infection since depletion of p53 prior to infection of either immortalised or normal cells led to severely reduced late gene expression. The association of p53 with L4P is transient due to the action of products of L4P activity (L4-22K/33K), which establish a negative feedback loop that ensures the transient activity of L4P at the start of the late phase and contributes to an efficient switch from early to late phase virus gene expression.

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology > QR355 Virology
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Journal or Publication Title:	Journal of Virology
Publisher:	American Society for Microbiology
ISSN:	0022-538X
Official Date:	21 August 2013
Dates:	Date Event 21 August 2013 Published
Volume:	Volume 87
Number:	Number 21
Number of Pages:	9
Page Range:	pp. 11617-11625
DOI:	10.1128/JVI.01924-13
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	25 December 2015
Date of first compliant Open Access:	25 December 2015
Funder:	Wellcome Trust (London, England)
Grant number:	WT094713MA (WT)

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