Hydrogen sulfide is an antiviral and Antiinflammatory endogenous Gasotransmitter in the airways role in respiratory Syncytial virus infection

Teodora Ivanciuc, Elena Sbrana, Maria Ansar, Nikolay Bazhanov, Csaba Szabo, Antonella Casola, Roberto Garofalo

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Hydrogen sulfide (H2S) 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 H2S 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 H2S donor, for the prevention and treatment of RSV-induced lung disease, as well as to investigate the role of endogenous H2S in a mousemodel of RSV infection. Ten-to 12-week-old BALB/c mice treated with GYY4137, or C57BL/6J mice genetically deficient in the cystathionine g-lyase enzyme, the major H2S-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 H2S donor was associated with a significant reduction of viral-induced proinflammatory mediators and lung cellular infiltrates. Furthermore, cystathionine g-lyase-deficient mice showed significantly enhanced RSV-induced lung disease and viral replication compared with wild-Type animals. Overall, our results indicate that H2S 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.

Original languageEnglish (US)
Pages (from-to)684-696
Number of pages13
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume55
Issue number5
DOIs
StatePublished - Nov 1 2016

Fingerprint

Gasotransmitters
Respiratory Syncytial Virus Infections
Hydrogen Sulfide
Viruses
Respiratory Syncytial Viruses
Lung Diseases
Antiviral Agents
Anti-Inflammatory Agents
Pulmonary diseases
Cystathionine
Lyases
Viral Pneumonia
Tissue Donors
Lung
Bronchiolitis
Wild Animals
Enzymes
Inbred C57BL Mouse
Pharmacology
Transmitters

Keywords

  • Airway hyperresponsiveness
  • Antiviral
  • Cystathionine g-lyase
  • Lung injury
  • Paramyxovirus

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

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title = "Hydrogen sulfide is an antiviral and Antiinflammatory endogenous Gasotransmitter in the airways role in respiratory Syncytial virus infection",
abstract = "Hydrogen sulfide (H2S) 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 H2S 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 H2S donor, for the prevention and treatment of RSV-induced lung disease, as well as to investigate the role of endogenous H2S in a mousemodel of RSV infection. Ten-to 12-week-old BALB/c mice treated with GYY4137, or C57BL/6J mice genetically deficient in the cystathionine g-lyase enzyme, the major H2S-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 H2S donor was associated with a significant reduction of viral-induced proinflammatory mediators and lung cellular infiltrates. Furthermore, cystathionine g-lyase-deficient mice showed significantly enhanced RSV-induced lung disease and viral replication compared with wild-Type animals. Overall, our results indicate that H2S 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.",
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author = "Teodora Ivanciuc and Elena Sbrana and Maria Ansar and Nikolay Bazhanov and Csaba Szabo and Antonella Casola and Roberto Garofalo",
year = "2016",
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T1 - Hydrogen sulfide is an antiviral and Antiinflammatory endogenous Gasotransmitter in the airways role in respiratory Syncytial virus infection

AU - Ivanciuc, Teodora

AU - Sbrana, Elena

AU - Ansar, Maria

AU - Bazhanov, Nikolay

AU - Szabo, Csaba

AU - Casola, Antonella

AU - Garofalo, Roberto

PY - 2016/11/1

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N2 - Hydrogen sulfide (H2S) 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 H2S 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 H2S donor, for the prevention and treatment of RSV-induced lung disease, as well as to investigate the role of endogenous H2S in a mousemodel of RSV infection. Ten-to 12-week-old BALB/c mice treated with GYY4137, or C57BL/6J mice genetically deficient in the cystathionine g-lyase enzyme, the major H2S-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 H2S donor was associated with a significant reduction of viral-induced proinflammatory mediators and lung cellular infiltrates. Furthermore, cystathionine g-lyase-deficient mice showed significantly enhanced RSV-induced lung disease and viral replication compared with wild-Type animals. Overall, our results indicate that H2S 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.

AB - Hydrogen sulfide (H2S) 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 H2S 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 H2S donor, for the prevention and treatment of RSV-induced lung disease, as well as to investigate the role of endogenous H2S in a mousemodel of RSV infection. Ten-to 12-week-old BALB/c mice treated with GYY4137, or C57BL/6J mice genetically deficient in the cystathionine g-lyase enzyme, the major H2S-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 H2S donor was associated with a significant reduction of viral-induced proinflammatory mediators and lung cellular infiltrates. Furthermore, cystathionine g-lyase-deficient mice showed significantly enhanced RSV-induced lung disease and viral replication compared with wild-Type animals. Overall, our results indicate that H2S 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.

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KW - Lung injury

KW - Paramyxovirus

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