Evidence map›Paper›PMID 29599452›Full record

ArticleScientific reports2018

Direct antiviral properties of TLR ligands against HBV replication in immune-competent hepatocytes.

Julie Lucifora, Marc Bonnin, Ludovic Aillot, Floriane Fusil, Sarah Maadadi, Laura Dimier, Maud Michelet, Océane Floriot, Anaïs Ollivier, Michel Rivoire and 7 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 2% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

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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

17 authors at 9 institutions in 3 countries.

Julie LuciforaINSERM, U1052, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL1), CNRS UMR_5286, Centre Léon Bérard, Lyon, France. julie.lucifora@inserm.fr.
Marc BonninINSERM, U1052, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL1), CNRS UMR_5286, Centre Léon Bérard, Lyon, France.
Ludovic AillotINSERM, U1052, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL1), CNRS UMR_5286, Centre Léon Bérard, Lyon, France.
Floriane FusilCIRI - International Center for Infectiology Research, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, F-69007, Lyon, France.
Sarah MaadadiINSERM, U1052, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL1), CNRS UMR_5286, Centre Léon Bérard, Lyon, France.
Laura DimierINSERM, U1052, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL1), CNRS UMR_5286, Centre Léon Bérard, Lyon, France.
Maud MicheletINSERM, U1052, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL1), CNRS UMR_5286, Centre Léon Bérard, Lyon, France.
Océane FloriotINSERM, U1052, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL1), CNRS UMR_5286, Centre Léon Bérard, Lyon, France.
Anaïs OllivierCIRI - International Center for Infectiology Research, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, F-69007, Lyon, France.
Michel RivoireINSERM U1032, Centre Léon Bérard (CLB), Lyon, France.
Malika Ait-GoughoulteRoche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche, 4070, Basel, Switzerland.
Stéphane DaffisGilead Sciences, Inc, Foster City, CA, USA.
Simon P FletcherGilead Sciences, Inc, Foster City, CA, USA.
Anna SalvettiINSERM, U1052, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL1), CNRS UMR_5286, Centre Léon Bérard, Lyon, France.
François-Loïc CossetCIRI - International Center for Infectiology Research, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, F-69007, Lyon, France.
Fabien ZoulimINSERM, U1052, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL1), CNRS UMR_5286, Centre Léon Bérard, Lyon, France.
David DurantelINSERM, U1052, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL1), CNRS UMR_5286, Centre Léon Bérard, Lyon, France. david.durantel@inserm.fr.
Centre de Recherche en Cancérologie de Lyon · FRCentre Léon Bérard · FRCentre National de la Recherche Scientifique · FRGilead Sciences (France) · FRInserm · FRCentre International de Recherche en Infectiologie · FRHôpital de la Croix-Rousse · FRRoche (Switzerland) · CHUniversité Claude Bernard Lyon 1 · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Current therapies for chronic hepatitis B virus (HBV) infections are effective at decreasing the viral load in serum, but do not lead to viral eradication. Recent studies highlighted the therapeutic or "adjuvant" potential of immune-modulators. Our aim was to explore the direct anti-HBV effect of Toll-Like-Receptors (TLR) agonists in hepatocytes. HBV-infected primary human hepatocytes (PHH) or differentiated HepaRG cells (dHepaRG) were treated with various TLR agonists. Amongst all TLR ligands tested, Pam3CSK4 (TLR1/2-ligand) and poly(I:C)-(HMW) (TLR3/MDA5-ligand) were the best at reducing all HBV parameters. No or little viral rebound was observed after treatment arrest, implying a long-lasting effect on cccDNA. We also tested Riboxxol that features improved TLR3 specificity compared to poly(I:C)-(HMW). This agonist demonstrated a potent antiviral effect in HBV-infected PHH. Whereas, poly(I:C)-(HMW) and Pam3CSK4 mainly induced the expression of classical genes from the interferon or NF-κB pathway respectively, Riboxxol had a mixed phenotype. Moreover, TLR2 and TLR3 ligands can activate hepatocytes and immune cells, as demonstrated by antiviral cytokines produced by stimulated hepatocytes and peripheral blood mononuclear cells. In conclusion, our data highlight the potential of innate immunity activation in the direct control of HBV replication in hepatocytes, and support the development of TLR-based antiviral strategies.

Indexed as

Antiviral AgentsHepatitis B virusHepatocytesHumansInterferonsLeukocytes, MononuclearLigandsLipopeptidesNF-kappa BToll-Like ReceptorsVirus ReplicationAntiviral AgentsInterferonsLigandsLipopeptidesNF-kappa BPam(3)CSK(4) peptideToll-Like Receptors

Identifiers

PMID29599452
PMCPMC5876392
OpenAlexW2807436290

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.