Human respiratory syncytial virus A2 strain replicates and induces innate immune responses by respiratory epithelia of neonatal lambs

A Olivier, J Gallup, MMMA De Macedo… - International journal …, 2009 - Wiley Online Library
A Olivier, J Gallup, MMMA De Macedo, SM Varga, M Ackermann
International journal of experimental pathology, 2009Wiley Online Library
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 …
Summary
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 6day 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 RSVinfected animals at day 6 postinoculation. There were no significant changes in sheep betadefensin‐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.
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