Inactivation of p53 rescues the maintenance of high risk HPV DNA genomes deficient in expression of E6.

The human papillomavirus DNA genome undergoes three distinct stages of replication: establishment, maintenance and amplification. We show that the HPV16 E6 protein is required for the maintenance of the HPV16 DNA genome as an extrachromosomal, nuclear plasmid in its natural host cell, the human kera...

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Autores principales:	Laurel D Lorenz, Jessenia Rivera Cardona, Paul F Lambert
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/783960713028493fa828ecde78f8218b
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spelling	oai:doaj.org-article:783960713028493fa828ecde78f8218b2021-11-18T06:07:26ZInactivation of p53 rescues the maintenance of high risk HPV DNA genomes deficient in expression of E6.1553-73661553-737410.1371/journal.ppat.1003717https://doaj.org/article/783960713028493fa828ecde78f8218b2013-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24204267/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The human papillomavirus DNA genome undergoes three distinct stages of replication: establishment, maintenance and amplification. We show that the HPV16 E6 protein is required for the maintenance of the HPV16 DNA genome as an extrachromosomal, nuclear plasmid in its natural host cell, the human keratinocyte. Based upon mutational analyses, inactivation of p53 by E6, but not necessarily E6-mediated degradation of p53, was found to correlate with the ability of E6 to support maintenance of the HPV16 genome as a nuclear plasmid. Inactivation of p53 with dominant negative p53 rescued the ability of HPV16 E6STOP and E6SAT mutant genomes to replicate as extrachromosomal genomes, though not to the same degree as observed for the HPV16 E6 wild-type (WT) genome. Inactivation of p53 also rescued the ability of HPV18 and HPV31 E6-deficient genomes to be maintained at copy numbers comparable to that of HPV18 and HPV31 E6WT genomes at early passages, though upon further passaging copy numbers for the HPV18 and 31 E6-deficient genomes lessened compared to that of the WT genomes. We conclude that inactivation of p53 is necessary for maintenance of HPV16 and for HPV18 and 31 to replicate at WT copy number, but that additional functions of E6 independent of inactivating p53 must also contribute to the maintenance of these genomes. Together these results suggest that re-activation of p53 may be a possible means for eradicating extrachromosomal HPV16, 18 or 31 genomes in the context of persistent infections.Laurel D LorenzJessenia Rivera CardonaPaul F LambertPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 10, p e1003717 (2013)
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 Laurel D Lorenz Jessenia Rivera Cardona Paul F Lambert Inactivation of p53 rescues the maintenance of high risk HPV DNA genomes deficient in expression of E6.
description	The human papillomavirus DNA genome undergoes three distinct stages of replication: establishment, maintenance and amplification. We show that the HPV16 E6 protein is required for the maintenance of the HPV16 DNA genome as an extrachromosomal, nuclear plasmid in its natural host cell, the human keratinocyte. Based upon mutational analyses, inactivation of p53 by E6, but not necessarily E6-mediated degradation of p53, was found to correlate with the ability of E6 to support maintenance of the HPV16 genome as a nuclear plasmid. Inactivation of p53 with dominant negative p53 rescued the ability of HPV16 E6STOP and E6SAT mutant genomes to replicate as extrachromosomal genomes, though not to the same degree as observed for the HPV16 E6 wild-type (WT) genome. Inactivation of p53 also rescued the ability of HPV18 and HPV31 E6-deficient genomes to be maintained at copy numbers comparable to that of HPV18 and HPV31 E6WT genomes at early passages, though upon further passaging copy numbers for the HPV18 and 31 E6-deficient genomes lessened compared to that of the WT genomes. We conclude that inactivation of p53 is necessary for maintenance of HPV16 and for HPV18 and 31 to replicate at WT copy number, but that additional functions of E6 independent of inactivating p53 must also contribute to the maintenance of these genomes. Together these results suggest that re-activation of p53 may be a possible means for eradicating extrachromosomal HPV16, 18 or 31 genomes in the context of persistent infections.
format	article
author	Laurel D Lorenz Jessenia Rivera Cardona Paul F Lambert
author_facet	Laurel D Lorenz Jessenia Rivera Cardona Paul F Lambert
author_sort	Laurel D Lorenz
title	Inactivation of p53 rescues the maintenance of high risk HPV DNA genomes deficient in expression of E6.
title_short	Inactivation of p53 rescues the maintenance of high risk HPV DNA genomes deficient in expression of E6.
title_full	Inactivation of p53 rescues the maintenance of high risk HPV DNA genomes deficient in expression of E6.
title_fullStr	Inactivation of p53 rescues the maintenance of high risk HPV DNA genomes deficient in expression of E6.
title_full_unstemmed	Inactivation of p53 rescues the maintenance of high risk HPV DNA genomes deficient in expression of E6.
title_sort	inactivation of p53 rescues the maintenance of high risk hpv dna genomes deficient in expression of e6.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/783960713028493fa828ecde78f8218b
work_keys_str_mv	AT laureldlorenz inactivationofp53rescuesthemaintenanceofhighriskhpvdnagenomesdeficientinexpressionofe6 AT jesseniariveracardona inactivationofp53rescuesthemaintenanceofhighriskhpvdnagenomesdeficientinexpressionofe6 AT paulflambert inactivationofp53rescuesthemaintenanceofhighriskhpvdnagenomesdeficientinexpressionofe6
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Inactivation of p53 rescues the maintenance of high risk HPV DNA genomes deficient in expression of E6.

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