Purinergic Signaling: A New Pharmacological Target Against Viruses?

Viral diseases represent a major global problem in human health, with high morbidity and mortality. Despite recent progress in antiviral treatments, several viral diseases are still not controlled and millions suffer from them every year. It has recently emerged that purinergic signaling participates in viral infection and replication. Furthermore, stimulation of purinergic receptors in infected cells also induces inflammatory and antiviral responses, thus contributing to the host antiviral defense. Here we review the multiple roles played by the purinergic signaling network in cell–virus interactions that can lead either to viral maintenance in the cells or, by contrast, to stronger antiviral responses, and discuss potential future applications of purinergic signaling modulation for the treatment of viral diseases. Highlights Viral infection induces the release of intracellular nucleotides (ATP, UTP) into the extracellular fluid. Autocrine activation of purinergic receptors expressed by host cells promotes viral entry and the replication of some viruses. Accordingly, inhibition of purinergic receptors impairs viral infection and the production of viral particles. Pharmacological stimulation of eukaryotic cells with ATP or massive nucleotide release due to extensive cell damage impairs cell–virus interaction and stimulates antiviral responses such as chemotaxis, transcription of antiviral cytokine genes, and the release of inflammatory mediators. Modulation of purinergic receptors expressed by immune cells might reduce the inflammatory responses and exacerbation of disease symptoms occurring as a consequence of the viral infection, such as in the case of asthma, cardiac inflammation, and neurological impairment, thus ameliorating the patient's condition. Targeting of purinergic signaling may represent a new possibility to control viral infections and the pathological consequences of viral diseases. [ABSTRACT FROM AUTHOR]