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Title: CLINICAL AND PATHOLOGICAL PARAMETERS OF PARAINFLUENZA VIRUS-3 INFECTION IN NEONATAL LAMBS WITH CONCURRENT ADENOVIRAL-MEDIATED BETA-DEFENSIN GENE THERAPY

Author
item MEYERHOLZ, D - IOWA STATE UNIVERSITY
item ANDERSON, R - VIRAQUEST INC
item HASKELL, R - VIRAQUEST INC
item Lehmkuhl, Howard
item GRUBOR, B - IOWA STATE UNIVERSITY
item GALLUP, J - IOWA STATE UNIVERSITY
item ACKERMANN, M - IOWA STATE UNIVERSITY

Submitted to: American College of Veterinary Pathologists Abstracts
Publication Type: Abstract Only
Publication Acceptance Date: 8/29/2003
Publication Date: 9/1/2003
Citation: MEYERHOLZ, D.K., ANDERSON, R.D., HASKELL, R.E., LEHMKUHL, H.D., GRUBOR, B.M., GALLUP, J.M., ACKERMANN, M.R. CLINICAL AND PATHOLOGICAL PARAMETERS OF PARAINFLUENZA VIRUS-3 INFECTION IN NEONATAL LAMBS WITH CONCURRENT ADENOVIRAL-MEDIATED BETA-DEFENSIN GENE THERAPY. AMERICAN COLLEGE OF VETERINARY PATHOLOGISTS ABSTRACTS. Vet. Pathol. 40:5, 603, Abstract #42.

Interpretive Summary:

Technical Abstract: Beta-defensins are a class of antimicrobial peptides with wide range of microbicidal activity, including enveloped viruses. The purpose of this experiment was to evaluate the clinical and pathological features of parainfluenza virus-3 (PIV-3) infection during co-inoculation of a non-replicative human adenovirus (Ad) with or without the human beta-defensin-6 (HBD-6) gene insert. Four groups of neonatal lambs (n=4/group, 3-5 days of age) were inoculated intratracheally (40cc/lamb) with: 1) sterile media, 2) PIV-3, 3) PIV-3/Ad or 4) PIV-3/Ad-HBD6. On day-1 post-inoculation (PI), rectal temperatures and respiratory rates were mildly increased in all lambs, especially groups 3-4. By day-2 PI, group 3 and 4 temperatures were reduced similar to group 2 and remained steady until increasing from day-4 PI until necropsy. At day-2 PI, respiration rates were similar in groups 2-4 with a gradual increased respiration rate starting day-3 PI and an elevated respiratory rate in group 4 on days 5 and 6 PI. Groups 2-4 had reduced average daily gain and milk consumption compared group 1 though the experiment. Subjective dyspnea scores gradually increased in group 2-4 from 1-day PI to necropsy. Gross lesions in groups 2-4 consisted of multifocal, hilar to cranial ventral plum-red consolidation and atelectasis. Affected bronchiolar epithelium was hyperplastic with rare necrotic foci. Bronchiolar lumens contained degenerate neutrophils, macrophages and sloughed epithelial cells. Adjacent alveolar septa were thickened by macrophages and neutrophils. Groups 3-4 had moderately increased numbers of bronchiolar luminal neutrophils compared to group 2. Adenoviral-mediated gene therapy during PIV-3 infection slightly enhanced lesion severity possibly due to increased antigenic exposure.