ArticleRetrovirology2008
Akt inhibitors as an HIV-1 infected macrophage-specific anti-viral therapy.
Article in Retrovirology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.
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Who cites it
76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 125 citations in OpenAlex.
- Meta-analysis of gene expression profiles in long-term non-progressors infected with HIV-1.BMC medical genomics · 2019Pooled it
- Host cell factors in HIV replication: meta-analysis of genome-wide studies.PLoS pathogens · 2009Pooled it
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- Dietary indoles influence the AHR-RORγt axis and mucosal immune homeostasis in ART-treated SIV infection.JCI insight · 2026Article
- Review
- HMC3 revealed: how much do these "Microglia" really tell us?Frontiers in immunology · 2026Review
- The effect of combining HIV latency reversal with inhibition of phosphoinositide-3 kinases or B-cell lymphoma-2 on the HIV reservoir.PLoS pathogens · 2026Article
- Enhanced Anti-Leukemic Activity of Platinum Lamivudine Compared To Lamivudine Through Differential Gene Regulation and DNA Groove Binding.Cell biochemistry and biophysics · 2025Article
- Host-directed approaches in the pursuit of a cure for HIV.Antiviral research · 2025Review
- Progress in antileishmanial drugs: Mechanisms, challenges, and prospects.PLoS neglected tropical diseases · 2025Review
- Mu opioid receptor activation in microglia enhances HIV-1 infection and HIV-infection-induced inflammatory responses.Frontiers in immunology · 2025Article
- The Proviral Reservoirs of Human Immunodeficiency Virus (HIV) Infection.Pathogens (Basel, Switzerland) · 2024Review
- YAP mediates HIV-related liver fibrosis.JHEP reports : innovation in hepatology · 2024Article
- Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR.Acta pharmacologica Sinica · 2024Article
- PTEN Mediates the Silencing of Unintegrated HIV-1 DNA.Viruses · 2024Article
- Antiviral Activity of Nitazoxanide and Miltefosine Against FeHV-1 In Vitro.Veterinary medicine international · 2024Article
- Occludin: a gatekeeper of brain Infection by HIV-1.Fluids and barriers of the CNS · 2023Review
- Nucleoside Analog 2',3'-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1.Pharmaceutics · 2023Article
- Revving the engine: PKB/AKT as a key regulator of cellular glucose metabolism.Frontiers in physiology · 2023Review
- RIOK3-Mediated Akt phosphorylation facilitates synergistic replication of Marek's disease and reticuloendotheliosis viruses.Virulence · 2022Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundUnlike CD4+ T cells, HIV-1 infected macrophages exhibit extended life span even upon stress, consistent with their in vivo role as long-lived HIV-1 reservoirs.
resultsHere, we demonstrate that PI3K/Akt inhibitors, including clinically available Miltefosine, dramatically reduced HIV-1 production from long-living virus-infected macrophages. These PI3K/Akt inhibitors hyper-sensitize infected macrophages to extracellular stresses that they are normally exposed to, and eventually lead to cell death of infected macrophages without harming uninfected cells. Based on the data from these Akt inhibitors, we were able to further investigate how HIV-1 infection utilizes the PI3K/Akt pathway to establish the cytoprotective effect of HIV-1 infection, which extends the lifespan of infected macrophages, a key viral reservoir. First, we found that HIV-1 infection activates the well characterized pro-survival PI3K/Akt pathway in primary human macrophages, as reflected by decreased PTEN protein expression and increased Akt kinase activity. Interestingly, the expression of HIV-1 or SIV Tat is sufficient to mediate this cytoprotective effect, which is dependent on the basic domain of Tat - a region that has previously been shown to bind p53. Next, we observed that this interaction appears to contribute to the downregulation of PTEN expression, since HIV-1 Tat was found to compete with PTEN for p53 binding; this is known to result in p53 destabilization, with a consequent reduction in PTEN protein production.
conclusionSince HIV-1 infected macrophages display highly elevated Akt activity, our results collectively show that PI3K/Akt inhibitors may be a novel therapy for interfering with the establishment of long-living HIV-1 infected reservoirs.
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What OpenQuestion holds
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.