Toll-like receptor dual-acting agonists are potent inducers of PBMC-produced cytokines that inhibit hepatitis B virus production in primary human hepatocytes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F20%3A00531566" target="_blank" >RIV/61388963:_____/20:00531566 - isvavai.cz</a>
Alternative codes found
RIV/68378050:_____/20:00541045 RIV/00216208:11310/20:10412943 RIV/00216208:11130/20:10412943 RIV/00023001:_____/20:00079968
Result on the web
<a href="https://doi.org/10.1038/s41598-020-69614-7" target="_blank" >https://doi.org/10.1038/s41598-020-69614-7</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41598-020-69614-7" target="_blank" >10.1038/s41598-020-69614-7</a>
Alternative languages
Result language
angličtina
Original language name
Toll-like receptor dual-acting agonists are potent inducers of PBMC-produced cytokines that inhibit hepatitis B virus production in primary human hepatocytes
Original language description
Recombinant interferon-α (IFN-α) treatment functionally cures chronic hepatitis B virus (HBV) infection in some individuals and suppresses virus replication in hepatocytes infected in vitro. We studied the antiviral effect of conditioned media (CM) from peripheral blood mononuclear cells (PBMCs) stimulated with agonists of Toll-like receptors (TLRs) 2, 7, 8 and 9. We found that CM from PBMCs stimulated with dual-acting TLR7/8 (R848) and TLR2/7 (CL413) agonists were more potent drivers of inhibition of HBe and HBs antigen secretion from HBV-infected primary human hepatocytes (PHH) than CM from PBMCs stimulated with single-acting TLR7 (CL264) or TLR9 (CpG-B) agonists. Inhibition of HBV in PHH did not correlate with the quantity of PBMC-produced IFN-α, but it was a complex function of multiple secreted cytokines. More importantly, we found that the CM that efficiently inhibited HBV production in freshly isolated PHH via various cytokine repertoires and mechanisms did not reduce covalently closed circular (ccc)DNA levels. We confirmed our data with a cell culture model based on HepG2-NTCP cells and the plasmacytoid dendritic cell line GEN2.2. Collectively, our data show the importance of dual-acting TLR agonists inducing broad cytokine repertoires. The development of poly-specific TLR agonists provides novel opportunities towards functional HBV cure.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10607 - Virology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Scientific Reports
ISSN
2045-2322
e-ISSN
—
Volume of the periodical
10
Issue of the periodical within the volume
Jul 29
Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
12767
UT code for WoS article
000556388300021
EID of the result in the Scopus database
2-s2.0-85088697271