ArticleNature2014
Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02563509 (Reconstitution of HIV-specific Immunity Against HIV), which is not on this map. Cited by 323 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Reconstitution of HIV-specific Immunity Against HIV
Who cites it
323 citing papers in PubMed, 1 synthesis or guideline pooled it, 462 citations in OpenAlex.
- The Hitchhiker Guide to CD4Frontiers in immunology · 2021Pooled it
- Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound.Scientific reports · 2022Trial
- Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption.The Journal of clinical investigation · 2020Trial
- Immunomodulation Induced During Interferon-α Therapy Impairs the Anti-HBV Immune Response Through CD24Frontiers in immunology · 2020Trial
- Schistosoma mansoni treatment reduces HIV entry into cervical CD4+ T cells and induces IFN-I pathways.Nature communications · 2019Trial
- The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon.Mucosal immunology · 2018Trial
- Type 1 interferon perturbates clonal competition by reshaping human blood development.Nature genetics · 2026Article
- Article
- Tenofovir, Interferon Pathways, and Mucosal Immunity: Implications for People Living With HIV.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Review
- Innate antiviral and immune functions associated with the HIV reservoir decay after anti-PD-1 therapy.Nature medicine · 2026Article
- Interferon-Based Therapeutics in Cancer Therapy: Past, Present, and Future.International journal of molecular sciences · 2025Review
- Treatment in acute HIV infection only temporarily preserves monocyte function: a comparative cohort study in adult males.EBioMedicine · 2025Article
- Chronic ISG15 Exposure Accelerates CD8+ T-cell Dysfunction while Increasing PD-1 Blockade Sensitivity in Oral Squamous Cell Carcinoma.Cancer immunology research · 2025Article
- Identification of AMOTL2 as an antiviral factor that enhances the human type I interferon response against Zika virus.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Establishment of a reverse genetics system for studying human immune functions in mice.Science advances · 2025Article
- Increased IFN responses drive myeloid cell activation in people living with HIV-1.Scientific reports · 2025Article
- Article
- Review
- Subtype AD Recombinant HIV-1 Transmitted/Founder Viruses Are Less Sensitive to Type I Interferons than Subtype D.Viruses · 2025Article
- Neurotransmitter and metabolic effects of interferon-alpha in association with decreased striatal dopamine in a non-human primate model of cytokine-Induced depression.Brain, behavior, and immunity · 2025Article
263 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
26 authors at 8 institutions in 2 countries.
Funding
Abstract
Inflammation in HIV infection is predictive of non-AIDS morbidity and death, higher set point plasma virus load and virus acquisition; thus, therapeutic agents are in development to reduce its causes and consequences. However, inflammation may simultaneously confer both detrimental and beneficial effects. This dichotomy is particularly applicable to type I interferons (IFN-I) which, while contributing to innate control of infection, also provide target cells for the virus during acute infection, impair CD4 T-cell recovery, and are associated with disease progression. Here we manipulated IFN-I signalling in rhesus macaques (Macaca mulatta) during simian immunodeficiency virus (SIV) transmission and acute infection with two complementary in vivo interventions. We show that blockade of the IFN-I receptor caused reduced antiviral gene expression, increased SIV reservoir size and accelerated CD4 T-cell depletion with progression to AIDS despite decreased T-cell activation. In contrast, IFN-α2a administration initially upregulated expression of antiviral genes and prevented systemic infection. However, continued IFN-α2a treatment induced IFN-I desensitization and decreased antiviral gene expression, enabling infection with increased SIV reservoir size and accelerated CD4 T-cell loss. Thus, the timing of IFN-induced innate responses in acute SIV infection profoundly affects overall disease course and outweighs the detrimental consequences of increased immune activation. Yet, the clinical consequences of manipulation of IFN signalling are difficult to predict in vivo and therapeutic interventions in human studies should be approached with caution.
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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.