Role of hydrogen sulfide in paramyxovirus infections.

UNLABELLED: Hydrogen sulfide (H2S) 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 H2S donor GYY4137 and propargylglycin (PAG), an inhibitor of cystathionine-γ-lyase (CSE), a key enzyme that produces intracellular H2S, we found that RSV infection led to a reduced ability to generate and maintain intracellular H2S 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 H2S 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 H2S 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. H2S antiviral and immunoregulatory properties could represent a novel treatment strategy for paramyxovirus infections. IMPORTANCE: RSV is a global health concern, causing significant morbidity and economic losses as well as mortality in developing countries. After decades of intensive research, no vaccine or effective treatment, with the exception of immunoprophylaxis, is available for this infection as well as for other important respiratory mucosal viruses. This study identifies hydrogen sulfide as a novel cellular mediator that can modulate viral replication and proinflammatory gene expression, both important determinants of lung injury in respiratory viral infections, with potential for rapid translation of such findings into novel therapeutic approaches for viral bronchiolitis and pneumonia.

Phototherapy in the treatment of cutaneous herpesvirus manifestations.

There is a considerable need for effective and safe treatment of cutaneous herpesvirus lesions. Current common approaches are limited to expensive or multidose oral pills. This systematic review of evidence-based approaches to phototherapy for the various manifestations of the herpesvirus discusses original publications of controlled clinical trials and case reports that were identified through searches in PubMed, MEDLINE, and Ovid. Interventions included photodynamic therapy (PDT), UV light, and near-infrared lasers. Nearly all studies (10 of 11) saw reduction of most or all lesions and extended time before reactivation of the virus. Side effects often were minimal to nonexistent, usually mild erythema at sites of phototreatment. Serious side effects included first-degree burns and linear IgA dermatosis, which were not common. Evidence from the reviewed literature indicates that short-term efficacy from treatment with phototherapy is the most likely outcome. However, long-term effects and follow-up of this treatment modality are lacking but appear promising. We recommend future studies to include more patients, determine the most effective type of phototherapy, and assess long-term follow-up. Furthermore, light-based therapies can be considered a reasonable alternative in situations that preclude traditional drug-based therapies.

A Polymorphism in the Catalase Gene Promoter Confers Protection against Severe RSV Bronchiolitis.

Respiratory syncytial virus (RSV) infection is associated with oxidative lung injury, decreased levels of antioxidant enzymes (AOEs), and the degradation of the transcription factor NF-E2-related factor 2 (NRF2), a master regulator of AOE expression. Single nucleotide polymorphisms (SNPs) in AOE and NRF2 genes have been associated with various lung disorders. To test whether specific NRF2 and/or AOE gene SNPs in children with RSV lower respiratory tract infection were associated with disease severity, one hundred and forty one children <24 month of age with bronchiolitis were assessed for seven AOE and two NRF2 SNPs, and data were correlated with disease severity, which was determined by need of oxygen supplementation and intensive care support. One SNP in the promoter region of the catalase gene, rs1001179, which is associated with higher enzyme expression, was significantly underrepresented (p = 0.01, OR 0.38) among patients with moderate to severe RSV bronchiolitis, suggesting a protective effect against disease severity. Our results suggest that increasing catalase expression/activity could exert a protective role in the context of RSV infection and represent a potential novel therapeutic target to ameliorate viral-induced lung disease.

Role of dietary antioxidants in human metapneumovirus infection.

Human metapneumovirus (hMPV) is a major cause of respiratory tract infections in children, elderly and immunocompromised hosts, for which no vaccine or treatment are currently available. Oxidative stress and inflammatory responses represent important pathogenic mechanism(s) of hMPV infection. Here, we explored the potential protective role of dietary antioxidants in hMPV infection. Treatment of airway epithelial cells with resveratrol and quercetin during hMPV infection significantly reduced cellular oxidative damage, inflammatory mediator secretion and viral replication, without affecting viral gene transcription and protein synthesis, indicating that inhibition of viral replication occurred at the level of viral assembly and/or release. Modulation of proinflammatory mediator expression occurred through the inhibition of transcription factor nuclear factor (NF)-κB and interferon regulatory factor (IRF)-3 binding to their cognate site of endogenous gene promoters. Our results indicate the use of dietary antioxidants as an effective treatment approach for modulating hMPV induced lung oxidative damage and inflammation.