This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lenaerts, L. Articles by Naesens, L. Search for Related Content PubMed PubMed Citation Articles by Lenaerts, L. Articles by Naesens, L.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2005, p. 4689-4699, Vol. 49, No. 11
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.11.4689-4699.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mouse Adenovirus Type 1 Infection in SCID Mice: an Experimental Model for Antiviral Therapy of Systemic Adenovirus Infections

Rega Institute for Medical Research, Division of Virology and Chemotherapy,¹ Division of Morphology and Molecular Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium²

Received 3 June 2005/ Returned for modification 15 July 2005/ Accepted 16 August 2005

The importance of human adenovirus infections in immunocompromised patients urges for new and adequate antiadenovirus compounds. Since human adenoviruses are species specific, animal models for systemic adenovirus infections rely on a nonhuman adenovirus. We established mouse adenovirus type 1 (MAV-1) infection of BALB/c SCID mice as a model for the evaluation of antiadenovirus therapy. In vitro studies with mouse embryonic fibroblasts pointed to the acyclic nucleoside phosphonate cidofovir and the N-7-substituted acyclic derivative 2-amino-7-(1,3-dihydroxy-2-propoxymethyl)purine (S-2242) as markedly active compounds against MAV-1. SCID mice, infected intranasally with MAV-1, developed a fatal disseminated infection after approximately 19 days, characterized by hemorrhagic enteritis. Several techniques were optimized to monitor viral, immunological, and pathological aspects of MAV-1 infection. Real-time PCR quantification of viral DNA revealed that after replication in the lungs, virus disseminated to several organs, including the brain, liver, spleen, intestine, heart, and kidneys (resulting in viruria). Immunohistochemical staining showed that MAV-1 was localized in the endothelial cells of the affected organs. Using reverse transcription-PCR, tissue levels of proinflammatory cytokines (i.e., interleukin-1ß and tumor necrosis factor alpha) were found to be markedly increased. The MAV-1/SCID model appears to be an appropriate model for in vivo evaluation of antiadenovirus agents. Treatment with cidofovir or S-2242 at a dose of 100 mg per kg of body weight resulted in a significant delay in MAV-1-related death, although these antivirals were unable to completely suppress virus replication despite continued drug treatment. These findings suggest that complete virus clearance during antiviral therapy for disseminated adenovirus infection may require an efficient adaptive immune response from the host.

This article has been cited by other articles:

• Lenaerts, L., Kelchtermans, H., Geboes, L., Matthys, P., Verbeken, E., De Clercq, E., Naesens, L. (2008). Recovery of Humoral Immunity Is Critical for Successful Antiviral Therapy in Disseminated Mouse Adenovirus Type 1 Infection. Antimicrob. Agents Chemother. 52: 1462-1471 [Abstract] [Full Text]  
• Dufner, A., Duncan, G. S., Wakeham, A., Elford, A. R., Hall, H. T., Ohashi, P. S., Mak, T. W. (2008). CARD6 Is Interferon Inducible but Not Involved in Nucleotide-Binding Oligomerization Domain Protein Signaling Leading to NF-{kappa}B Activation. Mol. Cell. Biol. 28: 1541-1552 [Abstract] [Full Text]