Trial reportPLoS pathogens2013
Type I interferon upregulates Bak and contributes to T cell loss during human immunodeficiency virus (HIV) infection.
Trial report in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 90 citations in OpenAlex.
- Heterologous Systems in the Functional Characterization of Proteins from Phytopathogenic Fungi: A Systematic Review.Molecular biotechnology · 2026Article
- Cell-Intrinsic Type I Interferon Signaling as a Pleiotropic Orchestrator of CD4 T Cell Immunity.Biomolecules · 2026Review
- Mechanisms and management of pegylated interferon-α toxicity in chronic hepatitis B.Frontiers in immunology · 2026Review
- Review
- KDM5A/B contribute to HIV-1 latent infection and survival of HIV-1 infected cells.Antiviral research · 2024Article
- IFNα Subtypes in HIV Infection and Immunity.Viruses · 2024Review
- IL-21-IgFc immunotherapy alters transcriptional landscape of lymph node cells leading to enhanced flu vaccine response in aging and SIV infection.Aging cell · 2023Article
- Recent Advances on Small-Molecule Antagonists Targeting TLR7.Molecules (Basel, Switzerland) · 2023Review
- T cell apoptosis characterizes severe Covid-19 disease.Cell death and differentiation · 2022Article
- Infection with HIV-1 subtype D among acutely infected Ugandans is associated with higher median concentration of cytokines compared to subtype A.IJID regions · 2022Article
- Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques.NPJ vaccines · 2022Article
- IFN-α blockade during ART-treated SIV infection lowers tissue vDNA, rescues immune function, and improves overall health.JCI insight · 2022Article
- Stratification of hospitalized COVID-19 patients into clinical severity progression groups by immuno-phenotyping and machine learning.Nature communications · 2022Article
- Tissue-specific transcriptional profiling of plasmacytoid dendritic cells reveals a hyperactivated state in chronic SIV infection.PLoS pathogens · 2021Article
- Rapid progression is associated with lymphoid follicle dysfunction in SIV-infected infant rhesus macaques.PLoS pathogens · 2021Article
- Investigational drugs with dual activity against HBV and HIV (Review).Experimental and therapeutic medicine · 2021Review
- Transcriptional and Immunologic Correlates of Response to Pandemic Influenza Vaccine in Aviremic, HIV-Infected Children.Frontiers in immunology · 2021Article
- Article
- Rapid in vitro generation of bona fide exhausted CD8+ T cells is accompanied by Tcf7 promotor methylation.PLoS pathogens · 2020Article
- Association between the cytokine storm, immune cell dynamics, and viral replicative capacity in hyperacute HIV infection.BMC medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
The role of Type I interferon (IFN) during pathogenic HIV and SIV infections remains unclear, with conflicting observations suggesting protective versus immunopathological effects. We therefore examined the effect of IFNα/β on T cell death and viremia in HIV infection. Ex vivo analysis of eight pro- and anti-apoptotic molecules in chronic HIV-1 infection revealed that pro-apoptotic Bak was increased in CD4+ T cells and correlated directly with sensitivity to CD95/Fas-mediated apoptosis and inversely with CD4+ T cell counts. Apoptosis sensitivity and Bak expression were primarily increased in effector memory T cells. Knockdown of Bak by RNA interference inhibited CD95/Fas-induced death of T cells from HIV-1-infected individuals. In HIV-1-infected patients, IFNα-stimulated gene expression correlated positively with ex vivo T cell Bak levels, CD95/Fas-mediated apoptosis and viremia and negatively with CD4+ T cell counts. In vitro IFNα/β stimulation enhanced Bak expression, CD95/Fas expression and CD95/Fas-mediated apoptosis in healthy donor T cells and induced death of HIV-specific CD8+ T cells from HIV-1-infected patients. HIV-1 in vitro sensitized T cells to CD95/Fas-induced apoptosis and this was Toll-like receptor (TLR)7/9- and Type I IFN-dependent. This sensitization by HIV-1 was due to an indirect effect on T cells, as it occurred in peripheral blood mononuclear cell cultures but not purified CD4+ T cells. Finally, peak IFNα levels and viral loads correlated negatively during acute SIV infection suggesting a potential antiviral effect, but positively during chronic SIV infection indicating that either the virus drives IFNα production or IFNα may facilitate loss of viral control. The above findings indicate stage-specific opposing effects of Type I IFNs during HIV-1 infection and suggest a novel mechanism by which these cytokines contribute to T cell depletion, dysregulation of cellular immunity and disease progression.
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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.