Background: Previous studies in mice showed that respiratory syncytial virus (RSV) infection was associated with RSV RNA persistence. This study was designed to characterize the significance of RSV RNA persistence and its relation to RSV-induced chronic airway disease.
Methods: Mice were inoculated with live RSV, UV light-treated RSV, heat-inactivated RSV, or medium. Bronchoalveolar lavage fluid samples were obtained and lung specimens were harvested on days 1, 5, and 42 after inoculation to assess lung inflammation, lung mRNA expression of interleukin (IL)-4, IL-5, IL-15, and interferon (IFN)-gamma; RSV loads were assessed by culture and real-time polymerase chain reaction (PCR) and correlated with pulmonary function.
Results: During the acute phase of infection, RSV loads as indicated by culture and PCR were significantly higher in mice inoculated with live RSV. On day 42, RSV RNA remained detectable only in mice inoculated with live or UV light-treated RSV. Lung inflammation, IFN-gamma:IL-4 mRNA expression ratios, airway obstruction (AO), and airway hyperreactivity (AHR) were significantly increased in mice inoculated with live RSV. AO on day 5 and AHR on day 42 were significantly correlated with RSV RNA copy number in lung samples.
Conclusions: Infection with live RSV induced acute and chronic airway disease that was associated with a predominantly Th-1 immune response and RSV RNA persistence that significantly correlated with pulmonary function abnormalities.
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http://dx.doi.org/10.1086/592714 | DOI Listing |
Viruses
January 2025
Department of Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Retroviral genome selection and virion assembly remain promising targets for novel therapeutic intervention. Recent studies have demonstrated that the Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus type-1 (HIV-1) undergo nuclear trafficking, colocalize with nascent genomic viral RNA (gRNA) at transcription sites, may interact with host transcription factors, and display biophysical properties characteristic of biomolecular condensates. In the present work, we utilized a controlled in vitro condensate assay and advanced imaging approaches to investigate the effects of interactions between RSV Gag condensates and viral and nonviral RNAs on condensate abundance and organization.
View Article and Find Full Text PDFJ Virol
January 2025
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
Human metapneumovirus (HMPV) is an important causative agent of respiratory tract disease. Fundamental knowledge of the interaction between HMPV and the innate immune system could lead to the design of novel antiviral therapies. Previously, we demonstrated that HMPV M2-2 deletion mutants had hypermutated genomes and contained defective interfering particles (DIs), which are potent inducers of the IFN response.
View Article and Find Full Text PDFbioRxiv
January 2025
Department of Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033.
Retroviruses are responsible for significant pathology in humans and animals, including the acquired immunodeficiency syndrome and a wide range of malignancies. A crucial yet poorly understood step in the replication cycle is the recognition and selection of unspliced viral RNA (USvRNA) by the retroviral Gag protein, which binds to the psi (Ψ) packaging sequence in the 5' leader, to package it as genomic RNA (gRNA) into nascent virions. It was previously thought that Gag initially bound gRNA in the cytoplasm.
View Article and Find Full Text PDFTher Adv Vaccines Immunother
January 2025
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, OX1 2JD, UK.
Respiratory syncytial virus (RSV) causes a significant burden of acute respiratory illness across all ages, particularly for infants and older adults. Infants, especially those born prematurely or with underlying health conditions, face a high risk of severe RSV-related lower respiratory tract infections (LRTIs). Globally, RSV contributes to millions of LRTI cases annually, with a disproportionate burden in low- and middle-income countries (LMICs).
View Article and Find Full Text PDFMolecules
December 2024
Institute of Organic and Analytical Chemistry (ICOA UMR 7311), CNRS, University of Orleans, F-45067 Orléans, France.
The emergence of RNA viruses driven by global population growth and international trade highlights the urgent need for effective antiviral agents that can inhibit viral replication. Nucleoside analogs, which mimic natural nucleotides, have shown promise in targeting RNA-dependent RNA polymerases (RdRps). Starting from protected 5-iodouridine, we report the synthesis of -substituted-(1,3-diyne)-uridines nucleosides and their phosphoramidate prodrugs.
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