Human herpesvirus 6B inhibits cell proliferation by a p53-independent pathway.
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.
Øster
Bodil
B
Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark.
Kaspersen
Maja D
MD
Kofod-Olsen
Emil
E
Bundgaard
Bettina
B
Höllsberg
Per
P
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
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