Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B.
Infection with human herpesvirus (HHV)-6B alters cell cycle progression and stabilizes tumor suppressor protein p53. In this study, we have analyzed the activity of p53 after stimulation with p53-dependent and -independent DNA damaging agents during HHV-6B infection. Microarray analysis, Western blo...
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oai:doaj.org-article:47cab761a6914845b4a9830b3b2071cd2021-11-18T07:52:03ZInhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B.1932-620310.1371/journal.pone.0059223https://doaj.org/article/47cab761a6914845b4a9830b3b2071cd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555634/?tool=EBIhttps://doaj.org/toc/1932-6203Infection with human herpesvirus (HHV)-6B alters cell cycle progression and stabilizes tumor suppressor protein p53. In this study, we have analyzed the activity of p53 after stimulation with p53-dependent and -independent DNA damaging agents during HHV-6B infection. Microarray analysis, Western blotting and confocal microscopy demonstrated that HHV-6B-infected cells were resistant to p53-dependent arrest and cell death after γ irradiation in both permissive and non-permissive cell lines. In contrast, HHV-6B-infected cells died normally through p53-independet DNA damage induced by UV radiation. Moreover, we identified a viral protein involved in inhibition of p53 during HHV-6B-infection. The protein product from the U19 ORF was able to inhibit p53-dependent signaling following γ irradiation in a manner similar to that observed during infection. Similar to HHV-6B infection, overexpression of U19 failed to rescue the cells from p53-independent death induced by UV radiation. Hence, infection with HHV-6B specifically blocks DNA damage-induced cell death associated with p53 without inhibiting the p53-independent cell death response. This block in p53 function can in part be ascribed to the activities of the viral U19 protein.Emil Kofod-OlsenJanni M L MøllerMariane H SchleimannBettina BundgaardRasmus O BakBodil ØsterJacob G MikkelsenTed HuppPer HöllsbergPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e59223 (2013) |
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Medicine R Science Q Emil Kofod-Olsen Janni M L Møller Mariane H Schleimann Bettina Bundgaard Rasmus O Bak Bodil Øster Jacob G Mikkelsen Ted Hupp Per Höllsberg Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B. |
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Infection with human herpesvirus (HHV)-6B alters cell cycle progression and stabilizes tumor suppressor protein p53. In this study, we have analyzed the activity of p53 after stimulation with p53-dependent and -independent DNA damaging agents during HHV-6B infection. Microarray analysis, Western blotting and confocal microscopy demonstrated that HHV-6B-infected cells were resistant to p53-dependent arrest and cell death after γ irradiation in both permissive and non-permissive cell lines. In contrast, HHV-6B-infected cells died normally through p53-independet DNA damage induced by UV radiation. Moreover, we identified a viral protein involved in inhibition of p53 during HHV-6B-infection. The protein product from the U19 ORF was able to inhibit p53-dependent signaling following γ irradiation in a manner similar to that observed during infection. Similar to HHV-6B infection, overexpression of U19 failed to rescue the cells from p53-independent death induced by UV radiation. Hence, infection with HHV-6B specifically blocks DNA damage-induced cell death associated with p53 without inhibiting the p53-independent cell death response. This block in p53 function can in part be ascribed to the activities of the viral U19 protein. |
format |
article |
author |
Emil Kofod-Olsen Janni M L Møller Mariane H Schleimann Bettina Bundgaard Rasmus O Bak Bodil Øster Jacob G Mikkelsen Ted Hupp Per Höllsberg |
author_facet |
Emil Kofod-Olsen Janni M L Møller Mariane H Schleimann Bettina Bundgaard Rasmus O Bak Bodil Øster Jacob G Mikkelsen Ted Hupp Per Höllsberg |
author_sort |
Emil Kofod-Olsen |
title |
Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B. |
title_short |
Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B. |
title_full |
Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B. |
title_fullStr |
Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B. |
title_full_unstemmed |
Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B. |
title_sort |
inhibition of p53-dependent, but not p53-independent, cell death by u19 protein from human herpesvirus 6b. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doaj.org/article/47cab761a6914845b4a9830b3b2071cd |
work_keys_str_mv |
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