Abstract
Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide. Many animal models are used to study RSV, but most studies investigate disease in adult animals which does not address the unique physiology and immunology that makes infants more susceptible. The perinatal (preterm and term) lamb is a useful model of infant RSV disease as lambs have similar pulmonary structure including airway branching, Clara and type II cells, submucosal glands and Duox/lactoperoxidase (LPO) oxidative system, and prenatal alveologenesis. Lambs can be born preterm (90% gestation) and survive for experimentation although both preterm and term lambs are susceptible to ovine, bovine and human strains of RSV and develop clinical symptoms including fever, tachypnea, and malaise as well as mild to moderate gross and histologic lesions including bronchiolitis with epithelial injury, neutrophil infiltration and syncytial cell formation. RSV disease in preterm lambs is more severe than in term lambs; disease is progressively less in adults and age-dependent susceptibility is a feature similar to humans. Innate and adaptive immune responses by perinatal lambs closely parallel those of infants. The model is used to test therapeutic regimens, risk factors such as maternal ethanol consumption, and formalin inactivated RSV vaccines.
Highlights
Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide [1]
Non-human primates, ferrets, cattle, and several other species have been utilized to study RSV; studies investigating disease in mature/adult animals fail to address the unique structure, cellularity, physiology, and immunology that contribute to the increased disease severity that can occur in perinatal infants infected with RSV
Dendritic cells are integral to immune response to RSV infection and increased numbers are present in nasal washes of infants with severe RSV [33]
Summary
Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide [1]. Risk factors of severe RSV disease in infants include premature birth, congenital heart defects, neuromuscular deficits, Down’s syndrome, immunodeficiency/compromise, and bronchopulmonary dysplasia [9–11]. Of these at-risk populations, the largest group is those born premature. The perinatal (preterm and term) lamb model has been used by several investigators to study RSV disease and paramyxoviral infections of infants as lambs have similar pulmonary development and are susceptible to ruminant and human strains of RSV and parainfluenza virus-3 [14–20]. Lambs develop mild clinical symptoms including fever, tachypnea or increased expiratory effort (wheeze), and malaise as well as mild to moderate gross and histologic lesions when experimentally infected with bovine (bRSV) or human (hRSV) strains of RSV [14–16,19,20]. The perinatal lamb model has a strong foundation and forms a valid model for RSV as evidenced by clinical alteration of respiration as well as gross and histologic lesions
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