Evidence map›Paper›PMID 24379396›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Inhibition of interferon gene activation by death-effector domain-containing proteins from the molluscum contagiosum virus.

Crystal M H Randall, Sunetra Biswas, Catherine V Selen, Joanna L Shisler

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

20 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Molluscum Contagiosum Virus: Biology and Immune Response.Advances in experimental medicine and biology · 2024
    Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. The Hippo Pathway and Viral Infections.Frontiers in microbiology · 2019
    Review
  10. Cellular FLIP long isoform (cFLIPThe Journal of biological chemistry · 2018
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  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

4 authors at 1 institution in 1 country.

Crystal M H RandallDepartment of Microbiology, College of Medicine, University of Illinois, Urbana, IL 61801.
Sunetra Biswas
Catherine V Selen
Joanna L Shisler
University of Illinois Urbana-Champaign · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Apoptosis, NF-κB activation, and IRF3 activation are a triad of intrinsic immune responses that play crucial roles in the pathogenesis of infectious diseases, cancer, and autoimmunity. FLIPs are a family of viral and cellular proteins initially found to inhibit apoptosis and more recently to either up- or down-regulate NF-κB. As such, a broad role for FLIPs in disease regulation is postulated, but exactly how a FLIP performs such multifunctional roles remains to be established. Here we examine FLIPs (MC159 and MC160) encoded by the molluscum contagiosum virus, a dermatotropic poxvirus causing skin infections common in children and immunocompromised individuals, to better understand their roles in viral pathogenesis. While studying their molecular mechanisms responsible for NF-κB inhibition, we discovered that each protein inhibited IRF3-controlled luciferase activity, identifying a unique function for FLIPs. MC159 and MC160 each inhibited TBK1 phosphorylation, confirming this unique function. Surprisingly, MC159 coimmunoprecipitated with TBK1 and IKKε but MC160 did not, suggesting that these homologs use distinct molecular mechanisms to inhibit IRF3 activation. Equally surprising was the finding that the FLIP regions necessary for TBK1 inhibition were distinct from those MC159 or MC160 regions previously defined to inhibit NF-κB or apoptosis. These data reveal previously unappreciated complexities of FLIPs, and that subtle differences within the conserved regions of FLIPs possess distinct molecular and structural fingerprints that define crucial differences in biological activities. A future comparison of mechanistic differences between viral FLIP proteins can provide new means of precisely manipulating distinct aspects of intrinsic immune responses.

Indexed as

HEK293 CellsHost-Pathogen InteractionsHumansI-kappa B KinaseImmunoblottingImmunoprecipitationInterferon-betaLuciferasesMolluscum ContagiosumMolluscum contagiosum virusNF-kappa BPhosphorylationProtein Serine-Threonine KinasesViral ProteinsI-kappa B KinaseInterferon-betaLuciferasesNF-kappa BProtein Serine-Threonine KinasesTBK1 protein, humanviral FLIP protein, Molluscum contagiosum virusViral Proteinshost–pathogen interactionsimmune evasion

Identifiers

PMID24379396
PMCPMC3896184
OpenAlexW2065806277

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.