Human cytomegalovirus inhibits cellular DNA synthesis and arrests productively infected cells in late G1

Wade A. Bresnahan, Istvan Boldogh, E. Aubrey Thompson, Thomas Albrecht

Research output: Contribution to journalArticle

180 Scopus citations

Abstract

Human embryonic lung fibroblasts (LU) can be productively infected h human cytomegalovirus (HCMV). During the course of productive infection, the virus elicits a number of responses that resemble certain aspects of G1 cell cycle progression. The virus activates cyclin E/Cdk2 kinase in both subconfluent, serum-arrested, and density-arrested cultures. Activation of cyclin E-dependent kinase is due, in part, to induction of cyclin E and, in part, to inhibition of the cyclin kinase inhibitors, Cip1 and Kip1. However, G1 progression is incomplete in HCMV-infected cells. Neither cyclin A nor cyclin D is induced, and cellular DNA synthesis does not occur if one takes care to avoid addition of fresh serum to serum-starved cultures. The data indicate that the virus induces a state of late G1 arrest, in which cyclin E/Cdk2 activates nucleotide metabolism and other biosynthetic processes that are necessary for viral replication. Failure to activate host cell DNA synthesis ensures that the virus will have uncompeted access to such precursors.

Original languageEnglish (US)
Pages (from-to)150-160
Number of pages11
JournalVirology
Volume224
Issue number1
DOIs
StatePublished - Oct 1 1996

ASJC Scopus subject areas

  • Virology

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