PMID:18234796
| Citation |
Zheng, X, Rao, XM, Gomez-Gutierrez, JG, Hao, H, McMasters, KM and Zhou, HS (2008) Adenovirus E1B55K region is required to enhance cyclin E expression for efficient viral DNA replication. J. Virol. 82:3415-27 |
|---|---|
| Abstract |
Adenoviruses (Ads) with E1B55K mutations can selectively replicate in and destroy cancer cells. However, the mechanism of Ad-selective replication in tumor cells is not well characterized. We have shown previously that expression of several cell cycle-regulating genes is markedly affected by the Ad E1b gene in WI-38 human lung fibroblast cells (X. Rao, et al., Virology 350:418-428, 2006). In the current study, we show that the Ad E1B55K region is required to enhance cyclin E expression and that the failure to induce cyclin E overexpression due to E1B55K mutations prevents viral DNA from undergoing efficient replication in WI-38 cells, especially when the cells are arrested in the G(0) phase of the cell cycle by serum starvation. In contrast, cyclin E induction is less dependent on the function encoded in the E1B55K region in A549 and other cancer cells that are permissive for replication of E1B55K-mutated viruses, whether the cells are in the S phase or G(0) phase. The small interfering RNA that specifically inhibits cyclin E expression partially decreased viral replication. Our study provides evidence suggesting that E1B55K may be involved in cell cycle regulation that is important for efficient viral DNA replication and that cyclin E overexpression in cancer cells may be associated with the oncolytic replication of E1B55K-mutated viruses. |
| Links |
PubMed PMC2268468 Online version:10.1128/JVI.01708-07 |
| Keywords |
Adenoviridae/genetics; Adenoviridae/physiology; Adenovirus E1B Proteins/genetics; Adenovirus E1B Proteins/physiology; Blotting, Western; Cell Line; Cyclin E/biosynthesis; DNA, Viral/biosynthesis; Fibroblasts/virology; Gene Silencing; Humans; RNA, Small Interfering/genetics; Virus Replication/genetics; Virus Replication/physiology |
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