The early region 1B 55-kilodalton oncoprotein of adenovirus relieves growth restrictions imposed on viral replication by the cell cycle

J Virol. 1997 Jan;71(1):548-61. doi: 10.1128/JVI.71.1.548-561.1997.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenovirus E1B Proteins / genetics
  • Adenovirus E1B Proteins / metabolism*
  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / metabolism*
  • Adenoviruses, Human / physiology
  • Cell Count
  • Cell Cycle*
  • DNA, Viral / biosynthesis
  • G1 Phase
  • HeLa Cells
  • Humans
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • S Phase
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism
  • Virion
  • Virus Replication

Substances

  • Adenovirus E1B Proteins
  • DNA, Viral
  • Oncogene Proteins
  • Tumor Suppressor Protein p53