title: Human respiratory syncytial virus A2 strain replicates and induces innate immune responses by respiratory epithelia of neonatal lambs.
abstract: Human respiratory syncytial virus (hRSV) is a pneumovirus that causes significant respiratory disease in premature and full-term infants. It was our hypothesis that a common strain of RSV, strain A2, would infect, cause pulmonary pathology, and alter respiratory epithelial innate immune responses in neonatal lambs similarly to RSV infection in human neonates. Newborn lambs between 2 and 3 days of age were inoculated intrabronchially with RSV strain A2. The lambs were sacrificed at days 3, 6, and 14 days postinoculation. Pulmonary lesions in the 6-day postinoculation group were typical of RSV infection including bronchiolitis with neutrophils and mild peribronchiolar interstitial pneumonia. RSV mRNA and antigen were detected by qPCR and immunohistochemistry, respectively with peak mRNA levels and antigen at day 6. Expression of surfactant proteins A and D, sheep beta-defensin-1 and thyroid transcription factor-1 mRNA were also assessed by real-time qPCR. There was a significant increase in surfactant A and D mRNA expression in RSV-infected animals at day 6 postinoculation. There were no significant changes in sheep beta-defensin-1 and thyroid transcription factor-1 mRNA expression. This study shows that neonatal lambs can be infected with RSV strain A2 and the pulmonary pathology mimics that of RSV infection in human infants thereby making the neonatal lamb a useful animal model to study disease pathogenesis and therapeutics. RSV infection induces increased expression of surfactant proteins A and D in lambs, which may also be an important feature of infection in newborn infants.
authors: Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA. aolivier@iastate.edu
authors: Alicia
authors: A
authors: Olivier
authors: Jack
authors: J
authors: Gallup
authors: Marcia M M A
authors: MM
authors: de Macedo
authors: Steven M
authors: SM
authors: Varga
authors: Mark
authors: M
authors: Ackermann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000956:Antigens, Viral / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D007113:Immunity, Innate; D007150:Immunohistochemistry; D023421:Models, Animal; D009687:Nuclear Proteins / Q000032:analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D037662:Pulmonary Surfactant-Associated Protein A / Q000032:analysis / Q000235:genetics; D037663:Pulmonary Surfactant-Associated Protein D / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D020545:Respiratory Mucosa / Q000276:immunology / Q000821:virology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000821:virology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology / Q000472:pathogenicity*; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology / Q000821:virology*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000032:analysis; D014779:Virus Replication; D023083:beta-Defensins / Q000032:analysis
chemical_list: D000956:Antigens, Viral; D015415:Biomarkers; C406407:DEFB1 protein, human; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D012333:RNA, Messenger; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D023083:beta-Defensins