title: Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B.
abstract: 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.
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Emil
authors.initials: E
authors.lastname: Kofod-Olsen
authors.forename: Janni M L
authors.initials: JM
authors.lastname: Møller
authors.forename: Mariane H
authors.initials: MH
authors.lastname: Schleimann
authors.forename: Bettina
authors.initials: B
authors.lastname: Bundgaard
authors.forename: Rasmus O
authors.initials: RO
authors.lastname: Bak
authors.forename: Bodil
authors.initials: B
authors.lastname: Øster
authors.forename: Jacob G
authors.initials: JG
authors.lastname: Mikkelsen
authors.forename: Ted
authors.initials: T
authors.lastname: Hupp
authors.forename: Per
authors.initials: P
authors.lastname: Höllsberg
mesh_terms: D016923:Cell Death / Q000528:radiation effects; D004249:DNA Damage; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000528:radiation effects; D045325:HCT116 Cells; D015654:Herpesvirus 6, Human / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D046228:Microarray Analysis; D015398:Signal Transduction / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins
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