Adenovirus E1B55K region is required to enhance cyclin E expression for efficient viral DNA replication.
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.
Zheng
Xinyu
X
James Graham Brown Cancer Center, University of Louisville School of Medicine, Baxter II, Room 321, 580 S. Preston St., Louisville, KY 40202, USA.
Rao
Xiao-Mei
XM
Gomez-Gutierrez
Jorge G
JG
Hao
Hongying
H
McMasters
Kelly M
KM
Zhou
H Sam
HS
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D019927:Cyclin E / Q000096:biosynthesis*; D004279:DNA, Viral / Q000096:biosynthesis*; D005347:Fibroblasts / Q000821:virology; D020868:Gene Silencing; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*
D017501:Adenovirus E1B Proteins; D019927:Cyclin E; D004279:DNA, Viral; D034741:RNA, Small Interfering