title: Human herpesvirus 6B inhibits cell proliferation by a p53-independent pathway.
abstract: BACKGROUND
  Various forms of cellular stress can activate the tumour suppressor protein p53, an important regulator of cell cycle arrest, apoptosis, and cellular senescence. Cells infected by human herpesvirus 6B (HHV-6B) accumulate aberrant amounts of p53.
  
  
  OBJECTIVE
  The aim of this study was to investigate the role of p53 accumulation in the HHV-6B-induced cell cycle arrest.
  
  
  METHODS
  The role of p53 was studied using the p53 inhibitor pifithrin-a, and cells genetically deficient in functional p53 by homologous recombination.
  
  
  RESULTS
  In response to HHV-6B infection, epithelial cells were arrested in the G1/S phase of the cell cycle concomitant with an aberrant accumulation of p53. However, the known p53-induced mediator of cell cycle arrest, p21, was not upregulated. Approximately 90% of the cells expressed HHV-6B p41, indicative of viral infection. The presence of pifithrin-a, a p53 inhibitor, did not reverse the HHV-6B-induced cell cycle block. In support of this, HHV-6B infection of p53(-/-) cells induced a cell cycle block before S-phase with kinetics similar to or faster than that observed by infection in wt cells.
  
  
  CONCLUSIONS
  HHV-6B infection inhibited host cell proliferation concomitantly with p53 accumulation, but importantly the block in cell cycle occurred by a pathway independent of p53.
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Bodil
authors.initials: B
authors.lastname: Øster
authors.forename: Maja D
authors.initials: MD
authors.lastname: Kaspersen
authors.forename: Emil
authors.initials: E
authors.lastname: Kofod-Olsen
authors.forename: Bettina
authors.initials: B
authors.lastname: Bundgaard
authors.forename: Per
authors.initials: P
authors.lastname: Höllsberg
mesh_terms: D052160:Benzothiazoles / Q000494:pharmacology; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication
chemical_list: D052160:Benzothiazoles; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; C081690:p41 protein, Human herpesvirus 6; D014050:Toluene; C121565:pifithrin