Efficient proliferation and mitosis of glioblastoma cells infected with human cytomegalovirus is mediated by RhoA GTPase

Al‑Qahtani,Ahmed A.; Alarifi,Saud; Alkahtani,Saad; Stournaras,Christos; Sourvinos,George

doi:10.3892/mmr.2020.11434

Efficient proliferation and mitosis of glioblastoma cells infected with human cytomegalovirus is mediated by RhoA GTPase

Authors:
- Ahmed A. Al‑Qahtani
- Saud Alarifi
- Saad Alkahtani
- Christos Stournaras
- George Sourvinos
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Affiliations: Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia, Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia, Department of Biochemistry, University of Crete, 71003 Heraklion, Greece, Laboratory of Clinical Virology, Medical School, University of Crete, 71003 Heraklion, Greece
Published online on: August 19, 2020 https://doi.org/10.3892/mmr.2020.11434
Pages: 3066-3072
Copyright: © Al‑Qahtani et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Human cytomegalovirus (HCMV) is a prevalent viral pathogen, which can cause severe clinical consequences in neonates, immunocompromised individuals, patients with AIDS, and organ and stem cell transplant recipients. HCMV inhibits the host cell cycle progress while the immediate‑early protein 1 (IE1) tethers to condensed chromatin in mitotic cells. The present study investigated the effect of HCMV on the cell cycle in human glioblastoma cells, as well as the role of RhoA GTPase during mitosis in the same context. Live cell microscopy showed that despite the apparent cell cycle arrest at late stages of mitosis in normal fibroblasts, HCMV‑infected U373MG cells successfully went through all stages of cell division. HCMV IE1 protein exhibited a remarkably tight association with mitotic chromosomes from early mitosis to late cytokinesis. Depletion of RhoA significantly impaired the proliferation rate of HCMV‑infected U373MG cells; consistent with this observation, the number of cells entering mitosis was also decreased. These results demonstrated the differential behavior of HCMV during mitosis in a normal and a cancer background. Furthermore, RhoA may be a critical component for the efficient cell division of HCMV‑infected glioblastoma cells, which subsequently ensures the maintenance of viral genomes.

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