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item Meyerholz, David
item Grubor, Branka
item Fach, Sasha
item Sacco, Randy
item Lehmkuhl, Howard
item Gallup, Jack
item Ackermann, Mark

Submitted to: Microbes and Infection
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/20/2004
Publication Date: 11/6/2004
Citation: Meyerholz, D.K., Grubor, B., Fach, S.J., Sacco, R.E., Lehmkuhl, H.D., Gallup, J.M., Ackermann, M.R. 2004. Reduced clearance of respiratory syncytial virus in a preterm lamb model. Microbes and Infection. 6(14):1312-1319.

Interpretive Summary: In the present journal article, we describe the development of a novel preterm lamb model of respiratory syncytial virus (RSV) infection. We delivered preterm lambs by caesarian section. The preterm lambs were more susceptible to infection than were full-term lambs infected during the first week of life. In addition, preterm lambs had more severe lesions than did full-term lambs. Our results suggest that the preterm lamb model should prove useful for assessing age-dependent mechanisms of severe RSV infection.

Technical Abstract: Respiratory syncytial virus (RSV) causes significant respiratory disease in children worldwide. For the study of severe RSV disease seen in preterm infants, a suitable animal model is lacking. The hypothesis of this study was that preterm lambs are susceptible to bovine RSV infection and that there would be age-dependent differences in select RSV disease parameters. During RSV infection, preterm lambs were pyrexic and tachypneic with mild anorexia and cough. Gross lesions included multifocal consolidation and atelectasis with foci of hyperinflation. Microscopic lesions included multifocal alveolar septal thickening and bronchiolitis. Immunohistochemistry localized the RSV antigen to all layers of bronchiolar epithelium from a few basal cells to numerous sloughing epithelia. Mononuclear cells were also immunoreactive. To assess for age-dependent differences in RSV infection, neonatal lambs were infected similarly to the preterm lambs or with a high-titer viral inoculum. Using morphometry at day 7 of infection, preterm lambs had significantly more cellular immunoreactivity for RSV antigen (p<0.05) and syncytial cell formation (p<0.05) than either group of neonatal lambs. This work suggests perinatal RSV clearance is age-dependent, which may explain the severity of RSV infection in preterm infants. The preterm lamb model is useful for assessing age-dependent mechanisms of severe RSV infection.