The early region 1B 55-kilodalton oncoprotein of adenovirus relieves growth restrictions imposed on viral replication by the cell cycle.
The E1B 55-kDa oncoprotein of adenovirus enables the virus to overcome restrictions imposed on viral replication by the cell cycle. Approximately 20% of HeLa cells infected with an E1B 55-kDa mutant adenovirus produced virus when evaluated by electron microscopy or by assays for infectious centers. By contrast, all HeLa cells infected with a wild-type adenovirus produced virus. The yield of E1B mutant virus from randomly cycling HeLa cells correlated with the fraction of cells in S phase at the time of infection. In synchronously growing HeLa cells, approximately 75% of the cells infected during S phase with the E1B mutant virus produced virus, whereas only 10% of the cells infected during G1 produced virus. The yield of E1B mutant virus from HeLa cells infected during S phase was sevenfold greater than that of cells infected during G1 and threefold greater than that of cells infected during asynchronous growth. Cells infected during S phase with the E1B mutant virus exhibited severe cytopathic effects, whereas cells infected with the E1B mutant virus during G1 exhibited a mild cytopathic effect. Viral DNA synthesis appeared independent of the cell cycle because equivalent amounts of viral DNA were synthesized in cells infected with either wild-type or E1B mutant virus. The inability of the E1B mutant virus to replicate was not mediated by the status of p53. These results define a novel property of the large tumor antigen of adenovirus in relieving growth restrictions imposed on viral replication by the cell cycle.
Goodrum
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Molecular Genetics Program, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1064, USA.
Ornelles
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D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002452:Cell Count; D002453:Cell Cycle; D004279:DNA, Viral / Q000096:biosynthesis; D016193:G1 Phase; D006367:HeLa Cells; D006801:Humans; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014771:Virion; D014779:Virus Replication
D017501:Adenovirus E1B Proteins; D004279:DNA, Viral; D015513:Oncogene Proteins; D016159:Tumor Suppressor Protein p53