AI Article Synopsis
- Current hepatitis B therapies lower viral levels but don't eliminate the virus, prompting research into immune-modulating treatments.
- The study examined the effects of various Toll-Like-Receptor (TLR) agonists on HBV-infected liver cells, finding that Pam3CSK4 and poly(I:C)-(HMW) were most effective at reducing viral indicators.
- The results suggest that activating innate immunity through TLR agonists may offer a new approach to directly control HBV replication, supporting further development of TLR-based antiviral therapies.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876392 | PMC |
| http://dx.doi.org/10.1038/s41598-018-23525-w | DOI Listing |
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