HDAC6 deacetylates TRIM56 to negatively regulate cGAS-STING-mediated type I interferon responses

EMBO Reports, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Histone deacetylase HDAC6 has been implicated in regulating antiviral innate immunity. However, its precise function response to DNA virus infection remains elusive. Herein, we find that deficiency promotes the activation of cGAS-STING signaling and type I interferon (IFN) production, both vitro vivo, resulting a decrease HSV-1 infection. Mechanistically, deacetylates tripartite motif protein 56 (TRIM56) at K110 mice, thereby impairing monoubiquitination cGAS binding ability. Overexpression TRIM56 K110Q protects mice against Notably, different amino acids position 110 human mouse cause species-specific IFN responses. Further, show during early stages infection, viral US3 phosphorylates inhibit cGAS-mediated response. Our results suggest inhibits through deacetylation manner.

Language: Английский

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Herpes simplex keratitis: A brief clinical overview

World Journal of Virology, Journal Year: 2024, Volume and Issue: 13(1)

Published: March 11, 2024

The aim of our minireview is to provide a brief overview the diagnosis, clinical aspects, treatment options, management, and current literature available regarding herpes simplex keratitis (HSK). This type corneal viral infection caused by virus (HSV), which can affect several tissues, including cornea. One significant aspect HSK its potential cause recurrent episodes inflammation damage After initial infection, HSV establish latent in trigeminal ganglion, nerve cluster near eye. may remain dormant for extended periods. Periodic reactivation occur, leading HSK. Factors triggering include stress, illness, immunosuppression, or trauma. Recurrent manifest different patterns, ranging from mild epithelial involvement more severe stromal endothelial disease. severity frequency recurrences vary among individuals. Severe cases HSK, especially those involving stroma scarring, result vision impairment even blindness extreme cases. cornea's clarity crucial good vision, scarring compromise this, potentially visual impairment. management involves not only treating acute but also implementing long-term strategies prevent attempt repairs endings via neurotization. Antiviral medications, such as oral Acyclovir topical Ganciclovir, be prescribed prophylaxis. immune response contribute damage. Inflammation, body's control inadvertently harm tissues. Clinicians should informed about triggers advised on measures minimize risk reactivation. In summary, nature underscores importance both preserve health maintain optimal function.

Language: Английский

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The Antiviral Potential of Perilla frutescens: Advances and Perspectives

Molecules, Journal Year: 2024, Volume and Issue: 29(14), P. 3328 - 3328

Published: July 15, 2024

Viruses pose a significant threat to human health, causing widespread diseases and impacting the global economy. Perilla frutescens, traditional medicine food homologous plant, is well known for its antiviral properties. This systematic review examines potential of including activity, chemical structure pharmacological parameters. Utilizing bioinformatics analysis, we revealed correlation between frutescens identified overlaps target genes virus-related genes, explored related signaling pathways. Moreover, classified summary active components focusing on compounds associated with provides important clues optimizing drug development frutescens. Our findings indicate that showed strong effect, ingredients can effectively inhibit replication spread variety viruses in this review. The mechanisms may involve several pathways, enhanced immune function, modulation inflammatory responses, inhibition key enzyme activities such as viral replicase. These results underscore application natural plant provide implications new drugs.

Language: Английский

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The combination of Schisandrin C and Luteolin synergistically attenuates hepatitis B virus infection via repressing HBV replication and promoting cGAS-STING pathway activation in macrophages

Chinese Medicine, Journal Year: 2024, Volume and Issue: 19(1)

Published: March 18, 2024

Abstract Background HBV infection can result in severe liver diseases and is one of the primary causes cell carcinoma-related mortality. Liuwei Wuling tablet (LWWL) a traditional Chinese medicine formula, with protecting decreasing enzyme activity, usually used to treat chronic hepatitis B NAs clinic. However, its main active ingredients mechanism action have not been fully investigated. Hence, we aimed screen ingredient effective combinations from explore anti-herpatitis virus activity mechanism. Methods Analysis screening antiviral components LWWL by network pharmacology, luteolin (Lut) may be compound significant activity. The Lut was also found real-time PCR detection western blotting. Meanwhile, established co-culture model investigate Schisandrin C (SC), Schisandra chinensis fructus (the sovereign drug LWWL). Next, HBV-infected mice were tail vein injection pAAV-HBV1.2 plasmid administered continuously for 20 days. And their capacity evaluated checking serum levels HBsAg, HBeAg, DNA, HBcAg. Results In this study, conducted pharmacology analysis on LWWL, through vitro experimental validation data analysis, that possessed obviously anti-HBV inhibiting replication downregulating hepatocyte nuclear factor 4α (HNF4α) via ERK pathway. Additionally, system proved SC promoted activation cGAS-STINIG pathway IFN-β production THP-1 cells inhibit HepG2.2.15 cells. Moreover, combination shows greater effect compared or alone mice. Conclusion Taken together, our study suggests potential candidate prevention treatment B.

Language: Английский

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An updated review of HSV-1 infection-associated diseases and treatment, vaccine development, and vector therapy application

Virulence, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 7, 2024

Herpes simplex virus type 1 (HSV-1) is a globally widespread that causes and associates with wide range of diseases, including herpes encephalitis, keratitis, labialis. The interaction between HSV-1 the host involves complex immune response mechanisms, recognition viral invasion, maintenance latent infection, triggering reactivation. Antiviral therapy core treatment for infections. Meanwhile, vaccine development employs different strategies methods, several promising types have emerged, such as live attenuated, protein subunit, nucleic acid vaccines, offering new possibilities prevention infection. Moreover, can be modified into therapeutic vector gene tumour immunotherapy. This review provides an in-depth summary infection-associated innate adaptive responses, disease pathogenesis, current approaches, recent advances in development, applications cancer treatment. Through systematic multiple aspects HSV-1, this study aims to provide comprehensive detailed reference public on prevention, control, HSV-1.

Language: Английский

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Antiviral Activity and Underlying Mechanism of Moslae Herba Aqueous Extract for Treating SARS-CoV-2

Molecules, Journal Year: 2025, Volume and Issue: 30(2), P. 387 - 387

Published: Jan. 17, 2025

Despite the widespread use of COVID-19 vaccines, there is still a global need to find effective therapeutics deal with variants SARS-CoV-2. Moslae herba (MH) herbal medicine credited antiviral effects. This study aims investigate effects and underlying mechanism aqueous extract (AEMH) for treating The in vitro anti-SARS-CoV-2 activity AEMH was evaluated using cell viability viral load. Component analysis performed by HPLC-ESI-Q-TOF/MS. connection between constructed integrating network pharmacology transcriptome profiles seek core targets. components activities were analyzed molecular docking pharmacological verification. exerted inhibiting replication reducing death caused infection (IC50 170 μg/mL omicron strain). A total 27 identified from AEMH. Through matching 119 intersection targets ‘disease drug’ 1082 differentially expressed genes patients, nine screened. Of nine, PNP TPI1 as treatment significantly regulated mRNA expression level two on infected cells. Three components, caffeic acid, luteolin, rosmarinic displayed Molecular also demonstrated they could form stable bonds explored possible SARS-CoV-2, which provide basic data reference clinical application MH.

Language: Английский

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Novel Hsp90α inhibitor inhibits HSV-1 infection by suppressing the Akt/β-catenin pathway

International Journal of Antimicrobial Agents, Journal Year: 2025, Volume and Issue: 65(3), P. 107448 - 107448

Published: Jan. 23, 2025

Language: Английский

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Regulation of Inflammatory Cytokines and Activation of PI3K/Akt Pathway by Yiqi Jiedu Formula in HSV-1-Induced Keratitis: Experimental and Network Pharmacology Evidence

Virus Research, Journal Year: 2025, Volume and Issue: unknown, P. 199561 - 199561

Published: March 1, 2025

Language: Английский

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Exogenous NADH promotes the bactericidal effect of aminoglycoside antibiotics against Edwardsiella tarda

Virulence, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 17, 2024

The global surge in multidrug-resistant bacteria owing to antibiotic misuse and overuse poses considerable risks human animal health. With existing antibiotics losing their effectiveness the protracted process of developing new antibiotics, urgent alternatives are imperative curb disease spread. Notably, improving bactericidal effect by using non-antibiotic substances has emerged as a viable strategy. Although reduced nicotinamide adenine dinucleotide (NADH) may play crucial role regulating bacterial resistance, studies examining how change metabolic profile resistance following exogenous administration scarce. Therefore, this study aimed elucidate changes that occur Edwardsiella tarda (E. tarda), which exhibits various addition NADH metabolomics. effects these alterations on activity neomycin were investigated. enhanced aminoglycoside against E. ATCC15947, achieving eradication at low doses. Metabolomic analysis revealed reprogrammed ATCC15947 promoting purine metabolism energy metabolism, yielding increased adenosine triphosphate (ATP) levels. Increased ATP levels played enhancing neomycin. Moreover, promoted efficacy tetracyclines chloramphenicols. combination with was effective other clinically resistant bacteria, including Aeromonas hydrophila, Vibrio parahaemolyticus, methicillin-resistant Staphylococcus aureus, Listeria monocytogenes. These results facilitate development approaches for preventing managing tarda–induced infections multidrug aquaculture clinical settings.

Language: Английский

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Anti-HSV-1 agents: an update

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 21, 2025

Herpes simplex virus type I (HSV-1) is a member of the α-herpesvirus subfamily and capable causing herpes keratitis, labialis, encephalitis. HSV-1 well known for its lytic infections at primary sites establishing latency in sensory neuronal ganglia, with occasional recurrent infections. To date, there are no approved commercially available vaccines, anti-HSV-1 drugs such as specific or non-specific nucleotide (nucleoside) analogs helicase-primase inhibitors have become main clinical agents treatment despite challenges from resistance. Therefore, development new compounds therapies key to addressing issue The present review provides an update on progress made over approximately 60 years regarding while also highlighting future perspectives controlling

Language: Английский

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