Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206

Kostritskaia, Yulia; Klüssendorf, Malte; Pan, Yingzhou Edward; Hassani Nia, Fatemeh; Kostova, Simona; Stauber, Tobias

doi:10.1007/164_2023_673

Handbook of Experimental Pharmacology

2023

DOI: 10.1007/164_2023_673

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Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206

Yulia Kostritskaia,

Malte Klüssendorf,

Yingzhou Edward Pan

et al.

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2024

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CFTR Inhibitors Display Antiviral Activity against Herpes Simplex Virus

Jiang,

Dai,

Yang

et al. 2024

Viruses

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The cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent Cl− channel, is closely associated with multiple pathogen infections, such as SARS-CoV-2. However, whether the function of the CFTR is involved in herpes simplex virus (HSV) infection has not been reported. To evaluate the association of CFTR activity with HSV infection, the antiviral effect of CFTR inhibitors in epithelial cells and HSV-infected mice was tested in this study. The data showed that treatment with CFTR inhibitors in different concentrations, Glyh-101 (5–20 μM), CFTRi-172 (5–20 μM) and IOWH-032 (5–20 μM), or the gene silence of the CFTR could suppress herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) replication in human HaCaT keratinocytes cells, and that a CFTR inhibitor, Glyh-101 (10–20 μM), protected mice from HSV-1 and HSV-2 infection. Intracellular Cl− concentration ([Cl−]i) was decreased after HSV infection via the activation of adenylyl cyclase (AC)-cAMP signaling pathways. CFTR inhibitors (20 μM) increased the reduced [Cl−]i caused by HSV infection in host epithelial cells. Additionally, CFTR inhibitors reduced the activity and phosphorylation of SGK1 in infected cells and tissues (from the eye and vagina). Our study found that CFTR inhibitors can effectively suppress HSV-1 and HSV-2 infection, revealing a previously unknown role of CFTR inhibitors in HSV infection and suggesting new perspectives on the mechanisms governing HSV infection in host epithelial cells, as well as leading to potential novel treatments.

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CFTR Inhibitors Display Antiviral Activity against Herpes Simplex Virus

Jiang,

Dai,

Yang

et al. 2024

Viruses

View full text Add to dashboard Cite

show abstract

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Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206

Cited by 1 publication

References 276 publications

CFTR Inhibitors Display Antiviral Activity against Herpes Simplex Virus

CFTR Inhibitors Display Antiviral Activity against Herpes Simplex Virus

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