Viral and cell cycle-regulated kinases in cytomegalovirus-induced pseudomitosis and replication

Laura Hertel, Sunwen Chou, Edward S. Mocarski

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

A process of pseudomitosis occurs during human cytomegalovirus infection that appears similar to cellular mitosis but involves the formation of multiple spindle poles, abnormal condensation, and mislocalization of chromosomal DNA. The relationship of this process to viral replication and cell cycle regulation during infection has been poorly understood. Pseudomitosis consistently peaks at late times of infection in all viral strains examined but at overall highest frequencies (30% to 35% of cells) using one common laboratory strain variant (AD169varATCC). Cyclin-dependent kinase 1 (Cdk1) plays a crucial role in pseudomitosis, mirroring its role in conventional mitosis. Dominant negative Cdk1 inhibits and wild-type Cdk1 stimulates this process; however, viral yields remain the same regardless of pseudomitosis levels. Broad inhibition of cell cycle-regulated kinases (Cdk1/Cdk2/Cdk5/Cdk9) with indirubin-3′-monoxime substantially decreases viral yields and synergizes with the viral UL97 kinase inhibitor, maribavir. Thus, Cdk1 is necessary and sufficient to drive pseudomitosis, whereas a combination of viral and cell cycle-regulated kinases is important during viral replication.

Original languageEnglish (US)
Pages (from-to)14-22
Number of pages9
JournalPLoS pathogens
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2007

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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