title: Restriction of human herpesvirus 6B replication by p53.
abstract: Human herpesvirus 6B (HHV-6B) induces significant accumulation of p53 in both the nucleus and cytoplasm during infection. Activation of p53 by DNA damage is known to induce either growth arrest or apoptosis; nevertheless, HHV-6B-infected cells are arrested in their cell cycle independently of p53, and only a minor fraction of the infected cells undergoes apoptosis. Using pifithrin-alpha, a p53 inhibitor, and p53-null cells, this study showed that infected epithelial cells accumulated viral transcripts and proteins to a significantly higher degree in the absence of active p53. Moreover, HHV-6B-induced cytopathic effects were greatly enhanced in the absence of p53. This suggests that, in epithelial cells, some of the functions of p53 leading to cell-cycle arrest and apoptosis are restrained by HHV-6B infection, whereas other cellular defences, causing inhibition of virus transcription, are partially retained.
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Bodil
authors.initials: B
authors.lastname: Øster
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Emil
authors.initials: E
authors.lastname: Kofod-Olsen
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Bettina
authors.initials: B
authors.lastname: Bundgaard
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Höllsberg
mesh_terms: D052160:Benzothiazoles / Q000494:pharmacology; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000821:virology; D015654:Herpesvirus 6, Human / Q000276:immunology*; D006801:Humans; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000502:physiology*; D014779:Virus Replication / Q000276:immunology*
chemical_list: D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D016159:Tumor Suppressor Protein p53; D014050:Toluene; C121565:pifithrin