Absence of an essential regulatory influence of the adenovirus E1B 19-kilodalton protein on viral growth and early gene expression in human diploid WI38, HeLa, and A549 cells

Abstract

Mutations in the gene encoding the adenovirus (Ad) early region 1B 19-kDa protein (the 19K gene) result in multiple phenotypic effects upon infection of permissive human cells. It has been reported, for example, that Ad type 2 (Ad2) and Ad5 with mutations in the 19K gene (19K-defective mutants) have a marked growth advantage compared with wild-type virus in human diploid W138 cells (E. White, B. Faha, and B. Stillman, Mol. Cell. Biol. 6:3763-3773, 1986), and it was proposed that this host range phenotype stems from the large increase in viral early gene expression reported to occur in the mutant-infected cells. These observations gave rise to the hypothesis that the 19-kDa protein (the 19K protein) normally functions as a negative regulator of Ad early gene expression and growth. We have tested this hypothesis and find that Ad5 and Adl2 wild-type viruses grow as efficiently as their respective 19K-defective mutants, inl and d1337 and pm700 and in700, in W138 and other human cell types. Neither the accumulation of ElA cytoplasmic mRNAs nor the synthesis of E1A and other viral early proteins in these cells is altered as a result of these mutations in the 19K gene, and we conclude that the 19K protein does not play an essential role in regulating viral early gene expression or viral growth in human cells.

Complete eradication of hepatomas using an oncolytic adenovirus containing AFP promoter controlling E1A and an E1B deletion to drive IL-24 expression

“…38,39 It was reported that the antiapoptotic gene E1B-19 kDa has a cell survival-promoting domain that is common to BCL-2 proteins, 40 and the E1B-19K protein does not play an essential role in regulating viral early gene expression or viral growth in human cancer cells, such as A549 and HeLa. 41 Deletion of E1B-19 kDa can remarkably increase the adenovirus cytolytic activity in 18 of 21 melanoma cells. 42 However, the E1B-55 kDa-deleted replicating adenovirus, ZD55, constructed in our laboratory, and OYNX-015, which had been in phase III clinical trials, have been noted for their ability to enhance the effects of chemotherapy, such as 5fluorouracil or cisplatin.…”