Summary auto-generated
Human cytomegalovirus (HCMV) is a pathogenic herpesvirus that manipulates cellular processes to facilitate viral replication. This study examined how HCMV alters the subcellular localization of Cdk2, a cell cycle regulatory protein normally sequestered in the cytoplasm of growth-arrested cells. Using human embryonic lung fibroblasts arrested by either serum deprivation or contact inhibition, researchers demonstrated that HCMV infection causes Cdk2 to translocate from the cytoplasm into the nucleus within 24 hours, similar to serum stimulation in serum-deprived cells. Notably, HCMV uniquely promoted Cdk2 nuclear translocation in contact-inhibited cells, where serum growth factors had no effect. Using UV-irradiated virus and immediate early protein staining, the authors showed that active viral gene expression is required for this Cdk2 translocation. The findings suggest HCMV overcomes growth-arrest constraints by inducing cyclin E/Cdk2 activation and nuclear localization, which the authors propose is essential for generating biosynthetic precursors needed for efficient viral replication in post-mitotic cells.
Key findings
- HCMV infection causes Cdk2 to translocate from the cytoplasm to the nucleus within 24 hours in both serum-deprived and contact-inhibited cells
- HCMV uniquely promotes Cdk2 nuclear translocation in contact-inhibited cells, whereas serum growth factors cannot overcome contact-inhibition
- Viral gene expression is required for Cdk2 translocation, as UV-irradiated virus lacking gene expression does not induce the effect
- Cdk2 is sequestered in the cytoplasm of both serum-arrested and contact-inhibited growth-arrested cells, representing a key constraint on cell cycle progression
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Abstract
Human cytomegalovirus (HCMV) stimulates numerous cellular pathways upon infection. One of these pathways involves activation of cyclin E/Cdk2. Recent reports have demonstrated that Cdk2 is retained in the cytoplasm of cells arrested in GO by serum deprivation, sequestered from its regulatory subunit cyclin E which is located within the nucleus. Cdk2 rapidly enters the nucleus and becomes active upon stimulation of these cells with serum growth factors. The ability of HCMV to activate cyclin E/Cdk2 in both serum-arrested cells and contact-inhibited cells suggests that HCMV infection may also result in the translocation of Cdk2 into the nucleus. In this report, we demonstrate that Cdk2 is sequestered in the cytoplasm of cells arrested in GO by contact inhibition, as well as those arrested by serum deprivation. HCMV infection results in translocation of Cdk2 from the cytoplasm into the nucleus within 24 h of infection, both in serum-arrested and contact- inhibited cells.