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Journal of Virology, April 2006, p. 3549-3558, Vol. 80, No. 7
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.7.3549-3558.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Replication Properties of Human Adenovirus In Vivo and in Cultures of Primary Cells from Different Animal Species

Christian Jogler,1,{dagger} Dennis Hoffmann,1 Dirk Theegarten,2,{ddagger} Thomas Grunwald,1 Klaus Überla,1 and Oliver Wildner1*

Ruhr-University Bochum, Department of Molecular and Medical Virology, Universitaetsstrasse 150, D-44801 Bochum, Germany,1 Ruhr-University Bochum, Institute of Pathology, Bürkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany2

Received 14 September 2005/ Accepted 28 December 2005

Oncolytic adenoviruses have emerged as a promising approach for the treatment of tumors resistant to other treatment modalities. However, preclinical safety studies are hampered by the lack of a permissive nonhuman host. Screening of a panel of primary cell cultures from seven different animal species revealed that porcine cells support productive replication of human adenovirus type 5 (Ad5) nearly as efficiently as human A549 cells, while release of infectious virus by cells from other animal species tested was diminished by several orders of magnitude. Restriction of productive Ad5 replication in rodent and rabbit cells seems to act primarily at a postentry step. Replication efficiency of adenoviral vectors harboring different E1 deletions or mutations in porcine cells was similar to that in A549 cells. Side-by-side comparison of the viral load kinetics in blood of swine and mice injected with Ad5 or a replication-deficient adenoviral vector failed to provide clear evidence for virus replication in mice. In contrast, evidence suggests that adenovirus replication occurs in swine, since adenoviral late gene expression produced a 13.5-fold increase in viral load in an individual swine from day 3 to day 7 and 100-fold increase in viral DNA levels in the Ad5-infected swine compared to the animal receiving a replication-deficient adenovirus. Lung histology of Ad5-infected swine revealed a severe interstitial pneumonia. Although the results in swine are based on a small number of animals and need to be confirmed, our data strongly suggest that infection of swine with human adenovirus or oncolytic adenoviral vectors is a more appropriate animal model to study adenoviral pathogenicity or pharmacodynamic and toxicity profiles of adenoviral vectors than infection of mice.

* Corresponding author. Mailing address: Department of Molecular and Medical Virology, Ruhr-University Bochum, Universitaetsstr. 150, Bldg. MA, Rm. 6-40, D-44801 Bochum, Germany. Phone: 49 234 32 27834. Fax: 49 234 32 14352. E-mail: Oliver.Wildner{at}ruhr-uni-bochum.de.

{dagger} Present address: Max Planck Institute for Marine Microbiology, Celciusstr. 1, 28359 Bremen, Germany.

{ddagger} Present address: Institute of Pathology and Neuropathology, University Clinic Essen, Hufelandstrasse 55, D-45122 Essen, Germany.

Journal of Virology, April 2006, p. 3549-3558, Vol. 80, No. 7
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.7.3549-3558.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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