Role of hydrogen sulfide in paramyxovirus infections

Hui Li, Yinghong Ma, Olivier Escaffre, Teodora Ivanciuc, Narayana Komaravelli, John P. Kelley, Ciro Coletta, Csaba Szabo, Barry Rockx, Roberto Garofalo, Antonella Casola

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Hydrogen sulfide (H<inf>2</inf>S) is an endogenous gaseous mediator that has gained increasing recognition as an important player in modulating acute and chronic inflammatory diseases. However, its role in virus-induced lung inflammation is currently unknown. Respiratory syncytial virus (RSV) is a major cause of upper and lower respiratory tract infections in children for which no vaccine or effective treatment is available. Using the slow-releasing H<inf>2</inf>S donor GYY4137 and propargylglycin (PAG), an inhibitor of cystathionine-γ-lyase (CSE), a key enzyme that produces intracellular H<inf>2</inf>S, we found that RSV infection led to a reduced ability to generate and maintain intracellular H<inf>2</inf>S levels in airway epithelial cells (AECs). Inhibition of CSE with PAG resulted in increased viral replication and chemokine secretion. On the other hand, treatment of AECs with the H<inf>2</inf>S donor GYY4137 reduced proinflammatory mediator production and significantly reduced viral replication, even when administered several hours after viral absorption. GYY4137 also significantly reduced replication and inflammatory chemokine production induced by human metapneumovirus (hMPV) and Nipah virus (NiV), suggesting a broad inhibitory effect of H<inf>2</inf>S on paramyxovirus infections. GYY4137 treatment had no effect on RSV genome replication or viral mRNA and protein synthesis, but it inhibited syncytium formation and virus assembly/release. GYY4137 inhibition of proinflammatory gene expression occurred by modulation of the activation of the key transcription factors nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3) at a step subsequent to their nuclear translocation. H<inf>2</inf>S antiviral and immunoregulatory properties could represent a novel treatment strategy for paramyxovirus infections.

Original languageEnglish (US)
Pages (from-to)5557-5568
Number of pages12
JournalJournal of Virology
Volume89
Issue number10
DOIs
StatePublished - 2015

Fingerprint

Respirovirus
Hydrogen Sulfide
hydrogen sulfide
cystathionine
viruses
Cystathionine
lyases
chemokines
virus replication
Infection
Lyases
infection
Respiratory Syncytial Viruses
Human metapneumovirus
epithelial cells
Chemokines
Nipah virus
Gasotransmitters
Nipah Virus
Epithelial Cells

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Li, H., Ma, Y., Escaffre, O., Ivanciuc, T., Komaravelli, N., Kelley, J. P., ... Casola, A. (2015). Role of hydrogen sulfide in paramyxovirus infections. Journal of Virology, 89(10), 5557-5568. https://doi.org/10.1128/JVI.00264-15

Role of hydrogen sulfide in paramyxovirus infections. / Li, Hui; Ma, Yinghong; Escaffre, Olivier; Ivanciuc, Teodora; Komaravelli, Narayana; Kelley, John P.; Coletta, Ciro; Szabo, Csaba; Rockx, Barry; Garofalo, Roberto; Casola, Antonella.

In: Journal of Virology, Vol. 89, No. 10, 2015, p. 5557-5568.

Research output: Contribution to journalArticle

Li, H, Ma, Y, Escaffre, O, Ivanciuc, T, Komaravelli, N, Kelley, JP, Coletta, C, Szabo, C, Rockx, B, Garofalo, R & Casola, A 2015, 'Role of hydrogen sulfide in paramyxovirus infections', Journal of Virology, vol. 89, no. 10, pp. 5557-5568. https://doi.org/10.1128/JVI.00264-15
Li H, Ma Y, Escaffre O, Ivanciuc T, Komaravelli N, Kelley JP et al. Role of hydrogen sulfide in paramyxovirus infections. Journal of Virology. 2015;89(10):5557-5568. https://doi.org/10.1128/JVI.00264-15
Li, Hui ; Ma, Yinghong ; Escaffre, Olivier ; Ivanciuc, Teodora ; Komaravelli, Narayana ; Kelley, John P. ; Coletta, Ciro ; Szabo, Csaba ; Rockx, Barry ; Garofalo, Roberto ; Casola, Antonella. / Role of hydrogen sulfide in paramyxovirus infections. In: Journal of Virology. 2015 ; Vol. 89, No. 10. pp. 5557-5568.
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