Search

Background: Data on how respiratory syncytial virus (RSV) genotypes influence disease severity and host immune responses is limited. Here, we characterized the genetic variability of RSV during 5 seasons, and evaluated the role of RSV subtypes, genotypes, and viral loads in disease severity and host transcriptional profiles.Methods: A prospective, observational study was carried out, including a convenience sample of healthy infants hospitalized with RSV bronchiolitis. Nasopharyngeal samples for viral load quantitation, typing, and genotyping, and blood samples for transcriptome analyses were obtained within 24 hours of hospitalization. Multivariate models were constructed to identify virologic and clinical variables predictive of clinical outcomes.Results: We enrolled 253 infants (median age 2.1 [25%-75% interquartile range] months). RSV A infections predominated over RSV B and showed greater genotype variability. RSV A/GA2, A/GA5, and RSV B/BA were the most common genotypes identified. Compared to GA2 or BA, infants with GA5 infections had higher viral loads. GA5 infections were associated with longer hospital stay, and with less activation of interferon and increased overexpression of neutrophil genes.Conclusions: RSV A infections were more frequent than RSV B, and displayed greater variability. GA5 infections were associated with enhanced disease severity and distinct host immune responses. [ABSTRACT FROM AUTHOR]

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)-γ; 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-γ: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. [ABSTRACT FROM AUTHOR]