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Synthetic Stimulator of Interferon Genes (STING) Agonists Induce a Cytokine-Mediated Anti-Hepatitis B Virus Response in Nonparenchymal Liver Cells
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SYSNO ASEP 0565954 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Synthetic Stimulator of Interferon Genes (STING) Agonists Induce a Cytokine-Mediated Anti-Hepatitis B Virus Response in Nonparenchymal Liver Cells Author(s) Pimková Polidarová, Markéta (UOCHB-X) ORCID
Vaneková, Lenka (UOCHB-X) ORCID
Břehová, Petra (UOCHB-X) RID, ORCID
Dejmek, Milan (UOCHB-X) RID, ORCID
Vavřina, Zdeněk (UOCHB-X) ORCID
Birkuš, Gabriel (UOCHB-X) ORCID
Brázdová, Andrea (UOCHB-X) ORCIDSource Title ACS Infectious Diseases. - : American Chemical Society - ISSN 2373-8227
Roč. 9, č. 1 (2023), s. 23-32Number of pages 10 s. Language eng - English Country US - United States Keywords chronic hepatitis B ; STING ; nonparenchymal liver cells ; antiviral immunity ; cytokine ; HBV-persistent mouse model OECD category Biochemistry and molecular biology R&D Projects EF16_019/0000729 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support UOCHB-X - RVO:61388963 UT WOS 000893678800001 EID SCOPUS 85143855156 DOI 10.1021/acsinfecdis.2c00424 Annotation Chronic hepatitis B (CHB) remains a major public health problem worldwide, with limited treatment options, but inducing an antiviral response by innate immunity activation may provide a therapeutic alternative. We assessed the cytokine-mediated anti-hepatitis B virus (HBV) potential for stimulating the cyclic GMP-AMP synthase-stimulator of interferon genes (STING) pathway using STING agonists in primary human hepatocytes (PHH) and nonparenchymal liver cells (NPCs). The natural STING agonist, 2',3'-cyclic GMP-AMP, the synthetic analogue 3',3'-c-di(2'F,2'dAMP), and its bis(pivaloyloxymethyl) prodrug had strong indirect cytokine-mediated anti-HBV effects in PHH regardless of HBV genotype. Furthermore, STING agonists induced anti-HBV cytokine secretion in vitro, in both human and mouse NPCs, and triggered hepatic T cell activation. Cytokine secretion and lymphocyte activation were equally stimulated in NPCs isolated from control and HBV-persistent mice. Therefore, STING agonists modulate immune activation regardless of HBV persistence, paving the way toward a CHB therapy. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2024 Electronic address https://doi.org/10.1021/acsinfecdis.2c00424
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