ArticleProceedings of the National Academy of Sciences of the United States of America2012
Role of retroviral restriction factors in the interferon-α-mediated suppression of HIV-1 in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. 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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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.
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Who cites it
89 citing papers in PubMed, 117 citations in OpenAlex.
- A novel mechanism linking memory stem cells with innate immunity in protection against HIV-1 infection.Scientific reports · 2017Trial
- Preservation of tetherin and CD4 counter-activities in circulating Vpu alleles despite extensive sequence variation within HIV-1 infected individuals.PLoS pathogens · 2014Trial
- Pegylated Interferon alfa-2a monotherapy results in suppression of HIV type 1 replication and decreased cell-associated HIV DNA integration.The Journal of infectious diseases · 2013Trial
- Intact type I Interferon production and IRF7 function in sooty mangabeys.PLoS pathogens · 2013Trial
- Review
- ZFP36L2 is an interferon β -induced inhibitor that restricts the nuclear export of HIV-1 transcripts.Nature communications · 2026Article
- Host-directed approaches in the pursuit of a cure for HIV.Antiviral research · 2025Review
- Interferons in HIV-1 infection: mechanisms, antiviral potentials, and therapeutic challenges.Frontiers in immunology · 2025Review
- Article
- Membrane Protein OTOF Is a Type I Interferon-Induced Entry Inhibitor of HIV-1 in Macrophages.mBio · 2022Article
- HIV-reservoir size is not affected either by HCV coinfection or by direct acting antivirals (DAAs) therapy.Scientific reports · 2022Article
- Mutagenic Activity of AID/APOBEC Deaminases in Antiviral Defense and Carcinogenesis.Molecular biology · 2022Article
- Article
- People with HIV-1 demonstrate type 1 interferon refractoriness associated with upregulated USP18.Journal of virology · 2021Article
- Mouse APOBEC3 Restriction of Retroviruses.Viruses · 2020Review
- The impact of bone marrow stromal antigen-2 (BST2) gene variants on HIV-1 control in black South African individuals.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020Article
- Understanding the mechanisms driving the spread of subtype C HIV-1.EBioMedicine · 2020Review
- An Alu Element Insertion in Intron 1 Results in Aberrant Alternative Splicing of APOBEC3G Pre-mRNA in Northern Pig-Tailed Macaques (Journal of virology · 2020Article
- Article
- Review
29 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 10 institutions in 2 countries.
Funding
Abstract
The antiviral potency of the cytokine IFN-α has been long appreciated but remains poorly understood. A number of studies have suggested that induction of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) and bone marrow stromal cell antigen 2 (BST-2/tetherin/CD317) retroviral restriction factors underlies the IFN-α-mediated suppression of HIV-1 replication in vitro. We sought to characterize the as-yet-undefined relationship between IFN-α treatment, retroviral restriction factors, and HIV-1 in vivo. APOBEC3G, APOBEC3F, and BST-2 expression levels were measured in HIV/hepatitis C virus (HCV)-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated IFN-α/ribavirin (IFN-α/riba) combination therapy. IFN-α/riba therapy decreased HIV-1 viral load by -0.921 (±0.858) log(10) copies/mL in HIV/HCV-coinfected patients. APOBEC3G/3F and BST-2 mRNA expression was significantly elevated during IFN-α/riba treatment in patient-derived CD4+ T cells (P < 0.04 and P < 0.008, paired Wilcoxon), and extent of BST-2 induction was correlated with reduction in HIV-1 viral load during treatment (P < 0.05, Pearson's r). APOBEC3 induction during treatment was correlated with degree of viral hypermutation (P < 0.03, Spearman's ρ), and evolution of the HIV-1 accessory protein viral protein U (Vpu) during IFN-α/riba treatment was suggestive of increased BST-2-mediated selection pressure. These data suggest that host restriction factors play a critical role in the antiretroviral capacity of IFN-α in vivo, and warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1-infected individuals.
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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.