title: The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis.
abstract: Respiratory syncytial virus (RSV) causes significant infant morbidity and mortality. For decades severe RSV-induced disease was thought to result from an uncontrolled host response to viral replication, but recent work suggests that a strong innate immune response early in infection is protective. To shed light on host-virus interactions and the viral determinants of disease, copy numbers of five RSV genes (NS1, NS2, N, G, F) were measured by quantitative real-time polymerase chain reaction (qPCR) in nasal wash samples from children with RSV-associated bronchiolitis. Correlations were sought with host cytokines/chemokines and biomarkers. Associations with disposition from the emergency department (hospitalized or sent home) and pulse oximetry O2 saturation levels were also sought. Additionally, RNase P copy number was measured and used to normalize nasal wash data. RSV gene copy numbers were found to significantly correlate with both cytokine/chemokine and biomarker levels; and RNase P-normalized viral gene copy numbers (NS1, NS2, N and G) were significantly higher in infants with less severe disease. Moreover, three of the normalized viral gene copy numbers (NS1, NS2, and N) correlated significantly with arterial O2 saturation levels. The data support a model where a higher viral load early in infection can promote a robust innate immune response that protects against progression into hypoxic RSV-induced lower respiratory tract illness.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Felipe-Andrés
authors.identifier: http://orcid.org/0000-0002-0100-2919
authors.initials: FA
authors.lastname: Piedra
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Minghua
authors.initials: M
authors.lastname: Mei
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Vasanthi
authors.identifier: http://orcid.org/0000-0003-4016-7588
authors.initials: V
authors.lastname: Avadhanula
authors.affiliation: Allergy & Asthma Specialists, P.C., Saddle River, New Jersey, United States of America.
authors.forename: Reena
authors.initials: R
authors.lastname: Mehta
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Letisha
authors.identifier: http://orcid.org/0000-0003-0490-4886
authors.initials: L
authors.lastname: Aideyan
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Roberto P
authors.identifier: http://orcid.org/0000-0001-7304-9698
authors.initials: RP
authors.lastname: Garofalo
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Pedro A
authors.identifier: http://orcid.org/0000-0002-5839-0879
authors.initials: PA
authors.lastname: Piedra
mesh_terms: D001988:Bronchiolitis / Q000175:diagnosis / Q000276:immunology* / Q000821:virology*; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D004636:Emergency Service, Hospital; D005260:Female; D006760:Hospitalization; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D063868:Patient Outcome Assessment; D018357:Respiratory Syncytial Virus Infections / Q000175:diagnosis / Q000276:immunology* / Q000821:virology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D012307:Risk Factors; D019562:Viral Load
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators