Evidence map›Paper›PMID 26529416›Full record

ArticlePLoS pathogens2015

Interferon-α Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms.

Michael S Harper, Kejun Guo, Kathrin Gibbert, Eric J Lee, Stephanie M Dillon, Bradley S Barrett, Martin D McCarter, Kim J Hasenkrug, Ulf Dittmer, Cara C Wilson and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
4.9field-weighted citation impact, top 4% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 98 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Interferon-Based Therapeutics in Cancer Therapy: Past, Present, and Future.International journal of molecular sciences · 2025
    Review
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  8. Article
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  18. Article
  19. Interferon resistance of emerging SARS-CoV-2 variants.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  20. Article

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Michael S HarperDepartment of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America; Department of Immunology and Microbiology, University of Colorado Denver, Aurora, Colorado, United States of America.
Kejun GuoDepartment of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America.
Kathrin GibbertInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Eric J LeeDepartment of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America.
Stephanie M DillonDepartment of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America.
Bradley S BarrettDepartment of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America.
Martin D McCarterDepartment of Surgery, University of Colorado Denver, Aurora, Colorado, United States of America.
Kim J HasenkrugRocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Ulf DittmerInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Cara C WilsonDepartment of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America; Department of Immunology and Microbiology, University of Colorado Denver, Aurora, Colorado, United States of America.
Mario L SantiagoDepartment of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America; Department of Immunology and Microbiology, University of Colorado Denver, Aurora, Colorado, United States of America.
University of Colorado Denver · USUniversity of Duisburg-Essen · DENational Institutes of Health · US

Funding

Medical Scientist Training ProgramT32GM008497 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI WILSON, CARA C. · 1993 to 2022
$15.2M
HIV Infection in Humanized MiceZIAAI001141 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI HASENKRUG, KIM · 2011 to 2019
$4.2M
Role of Type I IFNs in Mucosal HIV-1 Immunity and PathogenesisR01AI134220 · NIAID · UNIVERSITY OF COLORADO DENVER · PI SANTIAGO, MARIO LUIS, WILSON, CARA C. · 2017 to 2021
$2.7M
Mechanisms of HIV-associated Gut T Cell DepletionR01AI108404 · NIAID · UNIVERSITY OF COLORADO DENVER · PI WILSON, CARA C. · 2013 to 2017
$2.3M
HIV-Associated Interferon Effector Mechanisms in the GALTR56AI116271 · NIAID · UNIVERSITY OF COLORADO DENVER · PI SANTIAGO, MARIO LUIS, WILSON, CARA C. · 2015 to 2015
$491k
Intramural NIH HHSNIAID NIH HHS R01 AI108404NIAID NIH HHS R01 AI134220NIAID NIH HHS R56 AI116271NIGMS NIH HHS T32 GM008497
6 · The paper itself

Abstract

HIV-1 is transmitted primarily across mucosal surfaces and rapidly spreads within the intestinal mucosa during acute infection. The type I interferons (IFNs) likely serve as a first line of defense, but the relative expression and antiviral properties of the 12 IFNα subtypes against HIV-1 infection of mucosal tissues remain unknown. Here, we evaluated the expression of all IFNα subtypes in HIV-1-exposed plasmacytoid dendritic cells by next-generation sequencing. We then determined the relative antiviral potency of each IFNα subtype ex vivo using the human intestinal Lamina Propria Aggregate Culture model. IFNα subtype transcripts from the centromeric half of the IFNA gene complex were highly expressed in pDCs following HIV-1 exposure. There was an inverse relationship between IFNA subtype expression and potency. IFNα8, IFNα6 and IFNα14 were the most potent in restricting HIV-1 infection. IFNα2, the clinically-approved subtype, and IFNα1 were both highly expressed but exhibited relatively weak antiviral activity. The relative potencies correlated with binding affinity to the type I IFN receptor and the induction levels of HIV-1 restriction factors Mx2 and Tetherin/BST-2 but not APOBEC3G, F and D. However, despite the lack of APOBEC3 transcriptional induction, the higher relative potency of IFNα8 and IFNα14 correlated with stronger inhibition of virion infectivity, which is linked to deaminase-independent APOBEC3 restriction activity. By contrast, both potent (IFNα8) and weak (IFNα1) subtypes significantly induced HIV-1 GG-to-AG hypermutation. The results unravel non-redundant functions of the IFNα subtypes against HIV-1 infection, with strong implications for HIV-1 mucosal immunity, viral evolution and IFNα-based functional cure strategies.

Indexed as

Antiviral AgentsCD4-Positive T-LymphocytesDendritic CellsHIV-1HIV InfectionsHumansInterferon-alphaVirionVirus ReplicationAntiviral AgentsInterferon-alpha

Identifiers

PMID26529416
PMCPMC4631339
OpenAlexW1953974801

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.