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Medical Microbiology and Immunology

, Volume 204, Issue 3, pp 409–419 | Cite as

Human cytomegalovirus riding the cell cycle

  • Deborah H. SpectorEmail author
Review
Part of the following topical collections:
  1. Cytomegalovirus

Abstract

Human cytomegalovirus (HCMV) infection modulates the host cell cycle to create an environment that is optimal for viral gene expression, DNA replication, and production of infectious virus. The virus mostly infects quiescent cells and thus must push the cell into G1 phase of the cell cycle to co-opt the cellular mechanisms that could be used for DNA synthesis. However, at the same time, cellular functions must be subverted such that synthesis of viral DNA is favored over that of the host. The molecular mechanisms by which this is accomplished include altered RNA transcription, changes in the levels and activity of cyclin-dependent kinases, and other proteins involved in cell cycle control, posttranslational modifications of proteins, modulation of protein stability through targeted effects on the ubiquitin–proteasome degradation pathway, and movement of proteins to different cellular locations. When the cell is in the optimal G0/G1 phase, multiple signaling pathways are altered to allow rapid induction of viral gene expression once negative factors have been eliminated. For the most part, the cell cycle will stop prior to initiation of host cell DNA synthesis (S phase), although many cell cycle proteins characteristic of the S/G2/M phase accumulate. The environment of a cell progressing through the cell cycle and dividing is not favorable for viral replication, and HCMV has evolved ways to sense whether cells are in S/G2 phase, and if so, to prevent initiation of viral gene expression until the cells cycle back to G1. A major target of HCMV is the anaphase-promoting complex E3 ubiquitin ligase, which is responsible for the ubiquitination and subsequent degradation of cyclins A and B and other cell cycle proteins at specific phases in the cell cycle. This review will discuss the effects of HCMV infection on cell cycle regulatory pathways, with the focus on selected viral proteins that are responsible for these effects.

Keywords

Human cytomegalovirus Cell cycle Anaphase-promoting complex Cyclins Cyclin-dependent kinases 

Notes

Acknowledgments

Research in the Spector laboratory was supported by NIH Grants CA073490 and AI0883991.

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© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Cellular and Molecular Medicine, The Skaggs School of Pharmacy and Pharmaceutical SciencesUniversity of California San DiegoLa JollaUSA

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