Antiviral innate immune response in non-myeloid cells is augmented by chloride ions via an increase in intracellular hypochlorous acid levels

• Published in: Scientific reports Vol. 8; no. 1; pp. 13630 - 11
• Main Authors: Ramalingam, Sandeep, Cai, Baiyi, Wong, Junsheng, Twomey, Matthew, Chen, Rui, Fu, Rebecca M, Boote, Toby, McCaughan, Hugh, Griffiths, Samantha J, Haas, Jürgen G
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 11.09.2018; Nature Publishing Group UK
• Subjects: A549 Cells; Aniline Compounds - pharmacology; Animals; Antiviral activity; Chloride; Chloride Channels - antagonists & inhibitors; Chloride Channels - immunology; Coronaviridae; Coronaviruses; Deoxyribonucleic acid; DNA; DNA biosynthesis; Epithelial cells; HeLa Cells; Herpes simplex; Humans; Hydrogen peroxide; Hydrogen Peroxide - immunology; Hypochlorous acid; Hypochlorous Acid - immunology; Immune response; Immunity, Innate; Influenza A; Innate immunity; Intracellular; Ions; Mice; Myeloid cells; NIH 3T3 Cells; Peroxidase; Peroxidase - antagonists & inhibitors; Peroxidase - immunology; Phagocytes; Phagolysosomes; Respiratory syncytial virus; Ribonucleic acid; RNA; RNA viruses; Sodium chloride; Sodium Chloride - immunology; Viruses; Viruses - immunology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-31936-y

Phagocytes destroy ingested microbes by producing hypochlorous acid (HOCl) from chloride ions (Cl ) and hydrogen peroxide within phagolysosomes, using the enzyme myeloperoxidase. HOCl, the active ingredient in bleach, has antibacterial/antiviral properties. As myeloperoxidase is needed for HOCl production, non-myeloid cells are considered incapable of producing HOCl. Here, we show that epithelial, fibroblast and hepatic cells have enhanced antiviral activity in the presence of increasing concentrations of sodium chloride (NaCl). Replication of enveloped/non-enveloped, DNA (herpes simplex virus-1, murine gammaherpesvirus 68) and RNA (respiratory syncytial virus, influenza A virus, human coronavirus 229E, coxsackievirus B3) viruses are inhibited in a dose-dependent manner. Whilst treatment with sodium channel inhibitors did not prevent NaCl-mediated virus inhibition, a chloride channel inhibitor reversed inhibition by NaCl, suggesting intracellular chloride is required for antiviral activity. Inhibition is also reversed in the presence of 4-aminobenzoic hydrazide, a myeloperoxidase inhibitor, suggesting epithelial cells have a peroxidase to convert Cl to HOCl. A significant increase in intracellular HOCl production is seen early in infection. These data suggest that non-myeloid cells possess an innate antiviral mechanism dependent on the availability of Cl to produce HOCl. Antiviral activity against a broad range of viral infections can be augmented by increasing availability of NaCl.