Evidence map›Paper›PMID 25297994›Full record

ArticleJournal of virology2014

Unabated adenovirus replication following activation of the cGAS/STING-dependent antiviral response in human cells.

Eric Lam, Erik Falck-Pedersen

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 14% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Infection and immunity · 2024
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Current Insights into the Host Immune Response to Respiratory Viral Infections.Advances in experimental medicine and biology · 2021
    Article
  18. Article
  19. Immunology of Adenoviral Vectors in Cancer Therapy.Molecular therapy. Methods & clinical development · 2019
    Review
  20. Article
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

2 authors at 1 institution in 1 country.

Eric LamWeill Medical College of Cornell University, Department of Microbiology and Immunology, Molecular Biology Graduate Program, New York, New York, USA.
Erik Falck-PedersenWeill Medical College of Cornell University, Department of Microbiology and Immunology, Molecular Biology Graduate Program, New York, New York, USA efalckp@med.cornell.edu.
Cornell University · US

Funding

Regulation of host cell inflammatory and maturation response through AdV DNAdeteR01AI094050 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI FALCK-PEDERSEN, ERIK S · 2011 to 2015
$2.1M
NCI NIH HHS CCSG CA020374NIAID NIH HHS R01 AI094050
6 · The paper itself

Abstract

unlabelledThe cGAS/STING DNA sensing complex has recently been established as a predominant pathogen recognition receptor (PRR) for DNA-directed type I interferon (IFN) innate immune activation. Using replication-defective adenovirus vectors and replication-competent wild-type adenovirus, we have modeled the influence of the cGAS/STING cascade in permissive human cell lines (A549, HeLa, ARPE19, and THP1). Wild-type adenovirus induced efficient early activation of the cGAS/STING cascade in a cell-specific manner. In all responsive cell lines, cGAS/STING short hairpin RNA (shRNA) knockdown resulted in a loss of TBK1 and interferon response factor 3 (IRF3) activation, a lack of beta interferon transcript induction, loss of interferon-dependent STAT1 activation, and diminished induction of interferon-stimulated genes (ISGs). Adenoviruses that infect through the coxsackievirus-adenovirus receptor (CAR) (Ad2 and Ad5) and the CD46 (Ad35) and desmoglein-2 (Ad7) viral receptors all induce the cGAS/STING/TBK1/IRF3 cascade. The magnitude of the IRF3/IFN/ISG antiviral response was strongly influenced by serotype, with Ad35>Ad7>Ad2. For each serotype, no enhancement of viral DNA replication or virus production occurred in cGAS or STING shRNA-targeted cell line pools. We found no replication advantage in permissive cell lines that do not trigger the cGAS/STING cascade following infection. The cGAS/STING/TBK1/IRF3 cascade was not a direct target of viral antihost strategies, and we found no evidence that Ad stimulation of the cGAS/STING DNA response had an impact on viral replication efficiency. IMPORTANCE: This study shows for the first time that the cGAS DNA sensor directs a dominant IRF3/IFN/ISG antiviral response to adenovirus in human cell lines. Activation of cGAS occurs with viruses that infect through different high-affinity receptors (CAR, CD46, and desmoglein-2), and the magnitude of the cGAS/STING DNA response cascade is influenced by serotype-specific functions. Furthermore, activation of the cGAS cascade occurred in a cell-specific manner. Activation of the cGAS/STING response did not impact viral replication, and viral immune evasion strategies did not target the cGAS/STING/TBK1/IRF3 cascade. These studies provide novel insight into the early innate recognition response to adenovirus.

Indexed as

Host-Pathogen InteractionsVirus ReplicationAdenoviruses, HumanCell LineCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseHumansInterferon Regulatory Factor-3Membrane ProteinsNucleotidyltransferasesProtein Serine-Threonine KinasesSTING ProteincGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseInterferon Regulatory Factor-3IRF3 protein, humanMembrane ProteinsNucleotidyltransferasesProtein Serine-Threonine KinasesSTING1 protein, humanSTING ProteinTBK1 protein, human

Identifiers

PMID25297994
PMCPMC4249147
OpenAlexW2058606390

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.