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.