Evidence map›Paper›PMID 20615867›Full record

ArticleThe Journal of biological chemistry2010

Innate immune signaling induces high levels of TC-specific deaminase activity in primary monocyte-derived cells through expression of APOBEC3A isoforms.

Beth K Thielen, John P McNevin, M Juliana McElrath, Brook Vander Stoep Hunt, Kevin C Klein, Jaisri R Lingappa

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

80 citing papers in PubMed, 104 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Qualitative and Quantitative Analysis of DNA Cytidine Deaminase Activity.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  14. Article
  15. Host-virus interaction and viral evasion.Cell biology international · 2021
    Review
  16. Article
  17. Host-directed editing of the SARS-CoV-2 genome.Biochemical and biophysical research communications · 2021
    Review
  18. Human Beta-Defensin 2 and 3 Inhibit HIV-1 Replication in Macrophages.Frontiers in cellular and infection microbiology · 2021
    Article
  19. APOBEC3A catalyzes mutation and drives carcinogenesis in vivo.The Journal of experimental medicine · 2020
    Article
  20. Article

20 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

6 authors at 2 institutions in 1 country.

Beth K ThielenDepartment of Global Health, University of Washington, Seattle, Washington 98102, USA.
John P McNevin
M Juliana McElrath
Brook Vander Stoep Hunt
Kevin C Klein
Jaisri R Lingappa
University of Washington · USFred Hutch Cancer Center · US

Funding

University of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4M
VENEREAL DISEASET32AI007140 · NIAID · UNIVERSITY OF WASHINGTON · PI Julia Cook Dombrowski · 1985 to 2026
$19.4M
Regulation of APOBEC3G enzymatic activity in HIV-infected primary human T cellsR01AI078781 · NIAID · UNIVERSITY OF WASHINGTON · PI LINGAPPA, JAISRI R · 2009 to 2012
$1.8M
NIAID NIH HHS R01 AI078781NIAID NIH HHS R01AI078781NIAID NIH HHS T32 AI007140NIGMS NIH HHS 5 T32 GM07266NIGMS NIH HHS T32 GM007266
6 · The paper itself

Abstract

In HIV-1-infected individuals, G-to-A hypermutation is found in HIV-1 DNA isolated from peripheral blood mononuclear cells (PBMCs). These mutations are thought to result from editing by one or more host enzymes in the APOBEC3 (A3) family of cytidine deaminases, which act on CC (APOBEC3G) and TC (other A3 proteins) dinucleotide motifs in DNA (edited cytidine underlined). Although many A3 proteins display high levels of deaminase activity in model systems, only low levels of A3 deaminase activity have been found in primary cells examined to date. In contrast, here we report high levels of deaminase activity at TC motifs when whole PBMCs or isolated primary monocyte-derived cells were treated with interferon-alpha (IFNalpha) or IFNalpha-inducing toll-like receptor ligands. Induction of TC-specific deaminase activity required new transcription and translation and correlated with the appearance of two APOBEC3A (A3A) isoforms. Knockdown of A3A in monocytes with siRNA abolished TC-specific deaminase activity, confirming that A3A isoforms are responsible for all TC-specific deaminase activity observed. Both A3A isoforms appear to be enzymatically active; moreover, our mutational studies raise the possibility that the smaller isoform results from internal translational initiation. In contrast to the high levels of TC-specific activity observed in IFNalpha-treated monocytes, CC-specific activity remained low in PBMCs, suggesting that A3G deaminase activity is relatively inhibited, unlike that of A3A. Together, these findings suggest that deaminase activity of A3A isoforms in monocytes and macrophages may play an important role in host defense against viruses.

Indexed as

Repetitive Sequences, Nucleic AcidAmino Acid SequenceAnimalsAPOBEC-3G DeaminaseBase SequenceCattleCell LineCytidine DeaminaseGene Expression Regulation, EnzymologicGene Knockdown TechniquesHumansImmunity, InnateInterferon-alphaMacrophagesMolecular Sequence DataMonocytesAPOBEC3A protein, humanAPOBEC-3G DeaminaseAPOBEC3G protein, humanCytidine DeaminaseInterferon-alphaProteinsRNA, Small InterferingToll-Like Receptors

Identifiers

PMID20615867
PMCPMC2934643
OpenAlexW2122540855

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.