Viral and Cell Cycle–Regulated Kinases in Cytomegalovirus-Induced Pseudomitosis and Replication

PLoS Pathogens

Edward S Mocarski¹  Laura Hertel²  Sunwen Chou³ 

[1] Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America;Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada;VA Medical Center, Portland, Oregon, United States of America

关键词: Viral replication;    Cell cycle;    cell division;    Kinase inhibitors;    Cell cycle inhibitors;    Cyclins;    Cytomegalovirus infection;    Protein kinases;    DNA replication;   

DOI  :  10.1371/journal.ppat.0030006

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY