Infectivity and expression of the early adenovirus proteins are important regulators of wild-type and DeltaE1B adenovirus replication in human cells.
An adenovirus mutant lacking the expression of the large E1B protein (DeltaE1B) has been reported to replicate selectively in cells lacking the expression of functionally wild-type (wt) p53. Based on these results the DeltaE1B or ONYX-015 virus has been proposed to be an oncolytic virus which might be useful to treat p53-deficient tumors. Recently however, contradictory results have been published indicating that p53-dependent cell death is required for productive adenovirus infection. Since there is an urgent need for new methods to treat aggressive, mutant p53-expressing primary tumors and their metastases we carefully examined adenovirus replication in human cells to determine whether or not the DeltaE1B virus can be used for tumor therapy. The results we present here show that not all human tumor cell lines take up adenovirus efficiently. In addition, we observed inhibition of the expression of adenovirus early proteins in tumor cells. We present evidence that these two factors rather than the p53 status of the cell determine whether adenovirus infection results in lytic cell death. Furthermore, the results we obtained by infecting a panel of different tumor cell lines show that viral spread of the DeltaE1B is strongly inhibited in almost all p53-proficient and -deficient cell lines compared to the wt virus. We conclude that the efficiency of the DeltaE1B virus to replicate efficiently in tumor cells is determined by the ability to infect cells and to express the early adenovirus proteins rather than the status of p53.
Steegenga
W T
WT
Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, Utrecht University, 3508 TA Utrecht, The Netherlands.
Riteco
N
N
Bos
J L
JL
D000256:Adenoviridae / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D006801:Humans; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D017501:Adenovirus E1B Proteins