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

Polidarová, Markéta Pimková; Vaneková, Lenka; Břehová, Petra; Dejmek, Milan; Vavřina, Zdeněk; Birkuš, Gabriel; Brázdová, Andrea

doi:10.1021/acsinfecdis.2c00424

Cited by 7 publications

(6 citation statements)

References 42 publications

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“…More specifically, innate immune evasion was halted and this led to the inhibition of HBV replication mediated by IFN-I secretion [ 149 , 207 ]. Additional in vitro studies using three different STING agonists, cGAMP, 3′,3′-c-di(2′F,2′dAMP) and its bis(pivaloyloxymethyl) prodrug, corroborated that the activation of STING promotes viral clearance in human hepatocytes and non-parenchymal liver cells [ 208 ]. Similar effects were seen with the use of the topoisomerase II inhibitor daunorubicin, which activated the cGAS/STING pathway in vitro, suppressing HBV production [ 209 ].…”

Section: Targeting the Cgas/sting Associated Immune Evasion Mechanism...mentioning

confidence: 99%

STINGing Defenses: Unmasking the Mechanisms of DNA Oncovirus-Mediated Immune Escape

Martínez-López,

Muslin,

Kyriakidis

2024

Viruses

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DNA oncoviruses represent an intriguing subject due to their involvement in oncogenesis. These viruses have evolved mechanisms to manipulate the host immune response, facilitating their persistence and actively contributing to carcinogenic processes. This paper describes the complex interactions between DNA oncoviruses and the innate immune system, with a particular emphasis on the cGAS-STING pathway. Exploring these interactions highlights that DNA oncoviruses strategically target and subvert this pathway, exploiting its vulnerabilities for their own survival and proliferation within the host. Understanding these interactions lays the foundation for identifying potential therapeutic interventions. Herein, we sought to contribute to the ongoing efforts in advancing our understanding of the innate immune system in oncoviral pathogenesis.

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Section: Targeting the Cgas/sting Associated Immune Evasion Mechanism...mentioning

confidence: 99%

STINGing Defenses: Unmasking the Mechanisms of DNA Oncovirus-Mediated Immune Escape

Martínez-López,

Muslin,

Kyriakidis

2024

Viruses

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“…A TLR7 agonist (GS-9620) could activate interferon-stimulated genes (ISGs) and induce the production of IFN-a, as well as other cytokines and chemokines, which led to the clearance of HBV-infected cells (86). In phase 2 research, GS-9620 was well tolerated and safe in CHB patients, transcription of ISGs and serum cytokines was detected, and no clinically significant HBsAg decline was observed (102). Coincidentally, recent research has shown that HBV can disturb host cGAS DNA sensing to enhance the replication of HBV (103).…”

Section: Hbv-tg Mice Preclinicalmentioning

confidence: 99%

Abnormally primed CD8 T cells: The Achilles’ heel of CHB

Chen

Li²,

Jiang³

et al. 2023

Front. Immunol.

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Chronic hepatitis B virus (HBV) infection continues to be a significant public health challenge, and more than 250 million people around world are infected with HBV. The clearance of HBV with virus-specific CD8 T cells is critical for a functional cure. However, naïve HBV-specific CD8 T cells are heavily hindered during the priming process, and this phenomenon is closely related to abnormal cell and signal interactions in the complex immune microenvironment. Here, we briefly summarize the recent progress in understanding the abnormal priming of HBV-specific CD8 T cells and some corresponding immunotherapies to facilitate their functional recovery, which provides a novel perspective for the design and development of immunotherapy for chronic HBV infection (CHB). Finally, we also highlight the balance between viral clearance and pathological liver injury induced by CD8 T-cell activation that should be carefully considered during drug development.

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“…STING agonists play an important role as antivirals. A synthetic analog of 3’,3’-c-di(2’F,2’dAMP), 2’,3’-cyclic GMP-AMP, and its precursor pivaloyloxymethyl exert strong anti-hepatitis B virus (HBV) effects in primary human hepatocytes regardless of HBV genotype ( 104 ). Zhang X et al.…”

Section: Modulators Of the Cgas-sting Pathwaymentioning

confidence: 99%

The battle between the innate immune cGAS-STING signaling pathway and human herpesvirus infection

et al. 2023

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The incidence of human herpesvirus (HHVs) is gradually increasing and has affected a wide range of population. HHVs can result in serious consequences such as tumors, neonatal malformations, sexually transmitted diseases, as well as pose an immense threat to the human health. The cGAS-STING pathway is one of the innate immune pattern-recognition receptors discovered recently. This article discusses the role of the cGAS-STING pathway in human diseases, especially in human herpesvirus infections, as well as highlights how these viruses act on this pathway to evade the host immunity. Moreover, the author provides a comprehensive overview of modulators of the cGAS-STING pathway. By focusing on the small molecule compounds based on the cGAS-STING pathway, novel targets and concepts have been proposed for the development of antiviral drugs and vaccines, while also providing a reference for the investigation of disease models related to the cGAS-STING pathway. HHV is a double-stranded DNA virus that can trigger the activation of intracellular DNA sensor cGAS, after which the host cells initiate a cascade of reactions that culminate in the secretion of type I interferon to restrict the viral replication. Meanwhile, the viral protein can interact with various molecules in the cGAS-STING pathway. Viruses can evade immune surveillance and maintain their replication by inhibiting the enzyme activity of cGAS and reducing the phosphorylation levels of STING, TBK1 and IRF3 and suppressing the interferon gene activation. Activators and inhibitors of the cGAS-STING pathway have yielded numerous promising research findings in vitro and in vivo pertaining to cGAS/STING-related disease models. However, there remains a dearth of small molecule modulators that have been successfully translated into clinical applications, which serves as a hurdle to be overcome in the future.

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

Cited by 7 publications

References 42 publications

STINGing Defenses: Unmasking the Mechanisms of DNA Oncovirus-Mediated Immune Escape

STINGing Defenses: Unmasking the Mechanisms of DNA Oncovirus-Mediated Immune Escape

Abnormally primed CD8 T cells: The Achilles’ heel of CHB

The battle between the innate immune cGAS-STING signaling pathway and human herpesvirus infection

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