ArticleJournal of virology2002
Human cytomegalovirus major immediate-early proteins and simian virus 40 large T antigen can inhibit apoptosis through activation of the phosphatidylinositide 3'-OH kinase pathway and the cellular kinase Akt.
Article in Journal of virology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 148 citations in OpenAlex.
- Delivery of US28 by incoming HCMV particles rapidly attenuates Akt activity to suppress HCMV lytic replication in monocytes.Science signaling · 2024Article
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- Human cytomegalovirus attenuates AKT activity by destabilizing insulin receptor substrate proteins.bioRxiv : the preprint server for biology · 2023Article
- Human cytomegalovirus in cancer: the mechanism of HCMV-induced carcinogenesis and its therapeutic potential.Frontiers in cellular and infection microbiology · 2023Review
- Integrated analysis to study the interplay between post-translational modifications (PTM) in hepatitis C virus proteins and hepatocellular carcinoma (HCC) development.Scientific reports · 2022Article
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- The human cytomegalovirus decathlon: Ten critical replication events provide opportunities for restriction.Frontiers in cell and developmental biology · 2022Review
- Mechanisms of Survival of Cytomegalovirus-Infected Tumor Cells.Molecular biology · 2022Article
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- Autophagy impairment by African swine fever virus.The Journal of general virology · 2021Article
- The IGF-1 Signaling Pathway in Viral Infections.Viruses · 2021Review
- Viral Manipulation of the Host Epigenome as a Driver of Virus-Induced Oncogenesis.Microorganisms · 2021Review
- Non-covalent Interaction With SUMO Enhances the Activity of Human Cytomegalovirus Protein IE1.Frontiers in cell and developmental biology · 2021Article
- Tick-Borne Flaviviruses Depress AKT Activity during Acute Infection by Modulating AKT1/2.Viruses · 2020Article
- Strigolactone Analogs Are Promising Antiviral Agents for the Treatment of Human Cytomegalovirus Infection.Microorganisms · 2020Article
- Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function.Viruses · 2020Review
- SARS-CoV-2 and Glutamine: SARS-CoV-2 Triggered PathogenesisFrontiers in molecular biosciences · 2020Article
- P2Y2 purinergic receptor modulates virus yield, calcium homeostasis, and cell motility in human cytomegalovirus-infected cells.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- HCMV modulation of cellular PI3K/AKT/mTOR signaling: New opportunities for therapeutic intervention?Antiviral research · 2019Review
29 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The temperature-sensitive cell line ts13 is mutated in CCG1, the gene encoding TAF(II)250, the largest of the TATA-binding protein-associated factors (TAFs) in TFIID. At the nonpermissive temperature, the temperature-sensitive phenotypes are (i) transcription defects, (ii) cell cycle arrest in G(1), and (iii) apoptosis. We previously demonstrated that the human cytomegalovirus (HCMV) major immediate-early proteins (MIEPs) can rescue the transcription defects and inhibit apoptosis at the nonpermissive temperature. In the work presented, we show that activation of the cellular kinase Akt alone can inhibit apoptosis in ts13 cells grown at the nonpermissive temperature. More significantly, we show that the HCMV MIEPs can activate Akt, resulting in the inhibition of apoptosis. In parallel experiments, we found that simian virus 40 (SV40) large T antigen can mediate the same function. These experiments were done by transfecting the HCMV major immediate-early gene or a cDNA encoding T antigen into ts13 cells, and thus neither viral attachment to receptors, viral tegument proteins, nor any other viral protein is required for Akt activation. Akt is activated by the phosphatidylinositide 3'-OH (PI3) kinase pathway. Using a specific inhibitor of PI3 kinase, we show that the ability of the MIEPs and T antigen to activate Akt and inhibit apoptosis is eliminated, suggesting that the viral proteins utilize the PI3 kinase pathway for Akt activation. Transfection of plasmids which express the individual 86-kDa (IEP86; IE2(579aa)) and 72-kDa (IEP72; IE1(491aa)) MIEPs indicate that each MIEP could inhibit apoptosis via activation of the PI3 kinase pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.