Hydrogen Sulfide Is an Antiviral and Antiinflammatory Endogenous Gasotransmitter in the Airways. Role in Respiratory Syncytial Virus Infection

Abstract

Hydrogen sulfide (HS) is an endogenous gaseous transmitter whose role in the pathophysiology of several lung diseases has been increasingly appreciated. Our recent studies in vitro have shown, we believe for the first time, that HS has an important antiviral and antiinflammatory activity in respiratory syncytial virus (RSV) infection, the leading cause of bronchiolitis and viral pneumonia in children. Our objective was to evaluate the therapeutic potential of GYY4137, a novel slow-releasing HS donor, for the prevention and treatment of RSV-induced lung disease, as well as to investigate the role of endogenous HS in a mouse model of RSV infection. Ten- to 12-week-old BALB/c mice treated with GYY4137, or C57BL/6J mice genetically deficient in the cystathionine γ-lyase enzyme, the major HS-generating enzyme in the lung, were infected with RSV and assessed for viral replication, clinical disease, airway hyperresponsiveness, and inflammatory responses. Our results show that intranasal delivery of GYY4137 to RSV-infected mice significantly reduced viral replication and markedly improved clinical disease parameters and pulmonary dysfunction compared with the results in vehicle-treated control mice. The protective effect of the HS donor was associated with a significant reduction of viral-induced proinflammatory mediators and lung cellular infiltrates. Furthermore, cystathionine γ-lyase-deficient mice showed significantly enhanced RSV-induced lung disease and viral replication compared with wild-type animals. Overall, our results indicate that HS exerts a novel antiviral and antiinflammatory activity in the context of RSV infection and represent a potential novel pharmacological approach for ameliorating virus-induced lung disease.

Medical gases for stroke therapy: summary of progress 2015–2016

“…H 2 S is a signaling molecule and exert antioxidant, anti-inflammatory and vasodilatory actions 474849. These results lend credence to the notion that H 2 S provide neuroprotection in ischemic brain tissue.…”

Broad-Range Antiviral Activity of Hydrogen Sulfide Against Highly Pathogenic RNA Viruses

“…Recently, we demonstrated its effectiveness in paramyxovirus infections both in vitro 14 and in vivo 15. Exogenous administration of GYY4137 resulted in inhibition of both RSV replication and viral-induced production of pro-inflammatory cytokines and chemokines.…”

“…It was also associated with a reduction of pro-inflammatory mediator production, in a manner independent from inhibition of viral replication14. In a mouse model of RSV infection, administration of GYY4137 resulted in a significant reduction of lung viral titers and airway inflammation, and in an improvement of lung function and disease outcome15. In this study, we investigated whether H 2 S donor antiviral activity would extend to other RNA enveloped viruses.…”

Hydrogen sulfide in physiology and pathogenesis of bacteria and viruses

“…) . Moreover, H 2 S treatment significantly improved clinical disease parameters and pulmonary dysfunction on RSV infection . Similarly, H 2 S also exerts antiviral and anti‐inflammatory effects on the viruses in the family of Paramyxoviridae ; human metapneumovirus (hMPV) and Nipah virus (NiV) .…”