Synthetic Stimulator of Interferon Genes (STING) Agonists Induce a Cytokine-Mediated Anti-Hepatitis B Virus Response in Nonparenchymal Liver Cells

0565954 - ÚOCHB 2024 RIV US eng J - Journal Article
Pimková Polidarová, Markéta - Vaneková, Lenka - Břehová, Petra - Dejmek, Milan - Vavřina, Zdeněk - Birkuš, Gabriel - Brázdová, Andrea
Synthetic Stimulator of Interferon Genes (STING) Agonists Induce a Cytokine-Mediated Anti-Hepatitis B Virus Response in Nonparenchymal Liver Cells.
ACS Infectious Diseases. Roč. 9, č. 1 (2023), s. 23-32. ISSN 2373-8227
R&D Projects: GA MŠMT(CZ) EF16_019/0000729
Institutional support: RVO:61388963
Keywords : chronic hepatitis B * STING * nonparenchymal liver cells * antiviral immunity * cytokine * HBV-persistent mouse model
OECD category: Biochemistry and molecular biology
Impact factor: 5.3, year: 2022
Method of publishing: Limited access
https://doi.org/10.1021/acsinfecdis.2c00424

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.
Permanent Link: https://hdl.handle.net/11104/0337421