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CHARACTERIZATION OF RESPIRATORY DISEASE IN RATS FOLLOWING NEONATAL INOCULATION WITH A RAT-ADAPTED INFLUENZA VIRUS
Citation:
Dye, J., K. Morgan, D. Nelson, J. Tepper, G. Burleson, AND D. Costa. CHARACTERIZATION OF RESPIRATORY DISEASE IN RATS FOLLOWING NEONATAL INOCULATION WITH A RAT-ADAPTED INFLUENZA VIRUS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-96/065.
Description:
Neonatal F344 rats were infected with a rat-adapted influenza virus (RAIV) as a potential model to study the combined effects of early life viral respiratory infection with air pollutant dosimetry and toxic responses, as well as on the development of respiratory disease and increased airway responsiveness (AR). nitially, six-day-old pups were intranasally inoculated with RAIV or media alone, and nasal and lower respiratory tract tissues (LRT) were assessed histologically at 1, 3, 6, and 30 days-of-age), with histologic examination 6 and 13 days after the second inoculation, and bronchoprovocation testing 5-8 weeks later. ollowing the single RAIV inoculation, nasal histologic changes were evident as early as 1 DPI and primarily involved the anterior dorsal medial meatus and adjacent dorsal atrio- and nasoturbinates. lterations included epithelial cell exfoliation and necrosis, mild erosions, supportive and non supportive inflammation, intro-epithelial neutrophil accumulations, and intraluminal exudate. y 3 DPI, olfactory epithelial damage was multifocal or locally diffuse, with degeneration of sensory cells and variable inflammation. y 13 DPI, lesions were essentially repaired. inimal changes were apparent in the LRT despite evidence of viral replication in the trachea-lungs. ups reinoculated with RAIV at 30 days-of-age did not develop significant histologic lesions in spite of their immature immune status at the time of initial infection, nr)r did they exhibit increased AR when assessed as young adults. hus, neonatal RAIV infection resulted in acute nasal epithelial injury and inflammation, alterations which may allow subsequent evaluation of viral disease - air pollutant interactions.