ArticleJournal of immunology (Baltimore, Md. : 1950)2010
PI3K-dependent upregulation of Mcl-1 by human cytomegalovirus is mediated by epidermal growth factor receptor and inhibits apoptosis in short-lived monocytes.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 99 citations in OpenAlex.
- Critical role for antiapoptotic Bcl-xL and Mcl-1 in human macrophage survival and cellular IAP1/2 (cIAP1/2) in resistance to HIV-Vpr-induced apoptosis.The Journal of biological chemistry · 2012Trial
- UL45 of Human Cytomegalovirus Promotes Macrophage Survival and Modulates RIPK3-Associated Cell Death.Viruses · 2026Article
- A Potent Inhibitor of Human Cytomegalovirus Infection Works Post-Entry Specifically in Differentiating Myelo-Monocytic Cells.Pathogens (Basel, Switzerland) · 2026Article
- The PI3K/Akt Pathway in Herpesvirus Biology: A Double-Edged Sword in Host-Virus Interactions.Microorganisms · 2026Review
- Human cytomegalovirus-triggered necroptosis is suppressed by sequestration of MLKL in the nucleus of infected monocytes.Journal of virology · 2025Article
- Cytomegalovirus latency-the sum of subtleties.Journal of virology · 2025Review
- Human cytomegalovirus-IE2 suppresses antigen presentation of macrophage through the IL10/STAT3 signalling pathway in transgenic mouse.PloS one · 2025Article
- Inhibition of miR-20a promotes neural stem cell survival under oxidative stress conditions.Frontiers in neuroscience · 2025Article
- A landscape review with novel criteria to evaluate microbial drivers for cancer: priorities for innovative research targeting excessive cancer mortality in sub-Saharan Africa.Frontiers in cellular and infection microbiology · 2025Review
- Drugs Targeting Sirtuin 2 Exhibit Broad-Spectrum Anti-Infective Activity.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Delivery of US28 by incoming HCMV particles rapidly attenuates Akt activity to suppress HCMV lytic replication in monocytes.Science signaling · 2024Article
- Distinct early role of PTEN regulation during HCMV infection of monocytes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Human cytomegalovirus modulates mTORC1 to redirect mRNA translation within quiescently infected monocytes.Journal of virology · 2024Article
- Mcl-1 Protein and Viral Infections: A Narrative Review.International journal of molecular sciences · 2024Review
- Inhibition of SIRT2 promotes death of human cytomegalovirus-infected peripheral blood monocytes via apoptosis and necroptosis.Antiviral research · 2023Article
- Mechanisms of cancer cell death induction by paclitaxel: an updated review.Apoptosis : an international journal on programmed cell death · 2022Review
- Human Cytomegalovirus Manipulates Syntaxin 6 for Successful Trafficking and Subsequent Infection of Monocytes.Journal of virology · 2022Article
- Hypoxia Induces Autophagy in Human Dendritic Cells: Involvement of Class III PI3K/Vps34.Cells · 2022Article
- Review
- A Viral Long Non-Coding RNA Protects against Cell Death during Human Cytomegalovirus Infection of CD14+ Monocytes.Viruses · 2022Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Monocytes are a primary target for human CMV (HCMV) infection and are a key cell type responsible for hematogenous dissemination of the virus. Biologically, these cells have a short lifespan of 1-3 d in the circulation, yet infected cells remain viable for weeks despite the lack of viral antiapoptotic gene expression during this period. To understand the mechanism by which HCMV inhibits the initial phase of monocyte apoptosis, we focused on the viral modulation of early prosurvival cell signaling events after infection. We demonstrate in this study that the viral upregulation of the PI3K pathway promotes an early block in apoptosis after infection. Temporal transcriptome and protein analyses revealed Mcl-1, a member of the Bcl-2 family, was transiently induced in a PI3K-dependent manner during the early stages of HCMV infection. In accord with the survival studies, virally induced levels of Mcl-1 expression dissipated to mock levels by 72 h postinfection. Through the use of Mcl-1-specific small interfering RNA, we confirmed the functional role that Mcl-1 plays as a key early regulator of apoptosis in monocytes. Lastly, we showed that HCMV engagement and activation of the epidermal growth factor receptor during viral binding triggered the upregulation of Mcl-1. Overall, our data indicates that activation of the epidermal growth factor receptor/PI3K signaling pathway, via the PI3K-dependent upregulation of Mcl-1, is required to circumvent apoptosis in naturally short-lived monocytes during the early stages of HCMV infection, thus ensuring the early steps in the viral persistence strategy.
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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.