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

Laura Hertel, Sunwen Chou, Edward S. Mocarski

Research output: Contribution to journalArticle

42 Citations (Scopus)

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)
JournalPLoS Pathogens
Volume3
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

Fingerprint

CDC2 Protein Kinase
Cytomegalovirus
Cell Cycle
Phosphotransferases
Mitosis
Spindle Poles
Cytomegalovirus Infections
Infection
DNA

ASJC Scopus subject areas

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

Cite this

Viral and cell cycle-regulated kinases in cytomegalovirus-induced pseudomitosis and replication. / Hertel, Laura; Chou, Sunwen; Mocarski, Edward S.

In: PLoS Pathogens, Vol. 3, No. 1, 01.2007.

Research output: Contribution to journalArticle

@article{6ec86e8834e340abbd28754c48122d1e,
title = "Viral and cell cycle-regulated kinases in cytomegalovirus-induced pseudomitosis and replication.",
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.",
author = "Laura Hertel and Sunwen Chou and Mocarski, {Edward S.}",
year = "2007",
month = "1",
doi = "10.1371/journal.ppat.0030006",
language = "English (US)",
volume = "3",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Viral and cell cycle-regulated kinases in cytomegalovirus-induced pseudomitosis and replication.

AU - Hertel, Laura

AU - Chou, Sunwen

AU - Mocarski, Edward S.

PY - 2007/1

Y1 - 2007/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34250366295&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250366295&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.0030006

DO - 10.1371/journal.ppat.0030006

M3 - Article

VL - 3

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 1

ER -