ArticleAmerican journal of respiratory cell and molecular biology2007
Post-infection A77-1726 blocks pathophysiologic sequelae of respiratory syncytial virus infection.
Article in American journal of respiratory cell and molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Inhibitors of Nucleotide Biosynthesis as Candidates for a Wide Spectrum of Antiviral Chemotherapy.Microorganisms · 2022Review
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- SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport.American journal of physiology. Lung cellular and molecular physiology · 2021Article
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- Identification and Characterization of Novel Compounds with Broad-Spectrum Antiviral Activity against Influenza A and B Viruses.Journal of virology · 2020Article
- Pulmonary Deposition of Radionucleotide-Labeled Palivizumab: Proof-of-Concept Study.Frontiers in pharmacology · 2020Article
- Inhibiting pyrimidine biosynthesis impairs Ebola virus replication through depletion of nucleoside pools and activation of innate immune responses.Antiviral research · 2018Article
- Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae.American journal of physiology. Lung cellular and molecular physiology · 2017Review
- Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- TGF-β-induced IL-6 prevents development of acute lung injury in influenza A virus-infected F508del CFTR-heterozygous mice.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Selective targeting of alveolar type II respiratory epithelial cells by anti-surfactant protein-C antibody-conjugated lipoplexes.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- Deficiency of melanoma differentiation-associated protein 5 results in exacerbated chronic postviral lung inflammation.American journal of respiratory and critical care medicine · 2014Article
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- Radioprotection of lung tissue by soy isoflavones.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2013Article
- Heterozygosity for the F508del mutation in the cystic fibrosis transmembrane conductance regulator anion channel attenuates influenza severity.The Journal of infectious diseases · 2013Article
- Inhibition of pyrimidine biosynthesis pathway suppresses viral growth through innate immunity.PLoS pathogens · 2013Article
- Article
- Respiratory syncytial virus reverses airway hyperresponsiveness to methacholine in ovalbumin-sensitized mice.PloS one · 2012Article
- Immunosuppressive effects and mechanisms of leflunomide in dengue virus infection of human dendritic cells.Journal of clinical immunology · 2011Article
- Enhancement of alveolar epithelial sodium channel activity with decreased cystic fibrosis transmembrane conductance regulator expression in mouse lung.American journal of physiology. Lung cellular and molecular physiology · 2011Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Despite respiratory syncytial virus (RSV) bronchiolitis remaining the most common cause of lower respiratory tract disease in infants worldwide, treatment has progressed little in the past 30 years. The aim of our study was to determine whether post-infection administration of de novo pyrimidine synthesis inhibitors could prevent the reduction in alveolar fluid clearance (AFC) and hypoxemia that occurs at Day 2 after intranasal infection of BALB/c mice with RSV. BALB/c mice were infected intranasally with RSV strain A2. AFC was measured in anesthetized, ventilated mice after instillation of 5% bovine serum albumin into the dependent lung. Post-infection systemic treatment with leflunomide has no effect on AFC. However, when added to the AFC instillate, leflunomide's active metabolite, A77-1726, blocks RSV-mediated inhibition of AFC at Day 2. This block is reversed by uridine (which allows pyrimidine synthesis via the scavenger pathway) and not recapitulated by genistein (which mimics the tyrosine kinase inhibitor effects of A77-1726), indicating that the effect is specific for the de novo pyrimidine synthesis pathway. More importantly, when administered intranasally at Day 1, A77-1726, but not its vehicle dimethyl sulfoxide, maintains its beneficial effect on AFC and lung water content until Day 2. Intranasal instillation of A77-1726 at Day 1 also reduces bronchoalveolar lavage nucleotide levels, lung inflammation, and hypoxemia at Day 2 without impairing viral replication at Day 2 or viral clearance at Day 8. Post-infection intranasal or aerosolized treatment with pyrimidine synthesis inhibitors may provide symptomatic relief from the pathophysiologic sequelae of impaired AFC in children with RSV bronchiolitis.
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