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HAdV-C6 Is a More Relevant Challenge Virus than HAdV-C5 for Testing Antiviral Drugs with the Immunosuppressed Syrian Hamster Model

Adenovirus infections of immunocompromised patients can cause a severe multi-organ disease that often results in the patients’ death. Presently, there are no drugs specifically approved to treat adenovirus infections, and clinicians resort to the off-label use of antivirals that are approved to trea...

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Autores principales: Toth, Karoly, Spencer, Jacqueline F., Ying, Baoling, Tollefson, Ann E., Wold, William S. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490823/
https://www.ncbi.nlm.nih.gov/pubmed/28608847
http://dx.doi.org/10.3390/v9060147
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author Toth, Karoly
Spencer, Jacqueline F.
Ying, Baoling
Tollefson, Ann E.
Wold, William S. M.
author_facet Toth, Karoly
Spencer, Jacqueline F.
Ying, Baoling
Tollefson, Ann E.
Wold, William S. M.
author_sort Toth, Karoly
collection PubMed
description Adenovirus infections of immunocompromised patients can cause a severe multi-organ disease that often results in the patients’ death. Presently, there are no drugs specifically approved to treat adenovirus infections, and clinicians resort to the off-label use of antivirals that are approved to treat other DNA virus infections, most frequently cidofovir (CDV). CDV, however, has considerable nephrotoxicity, thus it is recommended only for the most severe cases of adenovirus infections. To facilitate the development of effective, non-toxic antivirals against adenovirus, we have developed a permissive animal model based on the Syrian hamster that can be used to test the efficacy of antiviral compounds. Here, we show that in the hamster model, HAdV-C6 is a more useful challenge virus than the previously described HAdV-C5, because it is filtered out by tissue macrophages to a lesser extent. HAdV-C6 has a 10-fold lower LD50 in hamsters than HAdV-C5 and the pathology is caused by virus replication to a larger extent. We show that valganciclovir (VGCV), a drug that was shown to be active against intravenous HAdV-C5 infection previously, is efficacious against HAdV-C6 when administered either prophylactically or therapeutically. Further, we show for the first time that VGCV, and to a lesser extent CDV, can be used to treat respiratory adenovirus infections in the hamster model. These results extend the utility of the hamster model, and demonstrate the efficacy of two drugs available for clinicians to treat adenovirus infections.
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spelling pubmed-54908232017-06-30 HAdV-C6 Is a More Relevant Challenge Virus than HAdV-C5 for Testing Antiviral Drugs with the Immunosuppressed Syrian Hamster Model Toth, Karoly Spencer, Jacqueline F. Ying, Baoling Tollefson, Ann E. Wold, William S. M. Viruses Article Adenovirus infections of immunocompromised patients can cause a severe multi-organ disease that often results in the patients’ death. Presently, there are no drugs specifically approved to treat adenovirus infections, and clinicians resort to the off-label use of antivirals that are approved to treat other DNA virus infections, most frequently cidofovir (CDV). CDV, however, has considerable nephrotoxicity, thus it is recommended only for the most severe cases of adenovirus infections. To facilitate the development of effective, non-toxic antivirals against adenovirus, we have developed a permissive animal model based on the Syrian hamster that can be used to test the efficacy of antiviral compounds. Here, we show that in the hamster model, HAdV-C6 is a more useful challenge virus than the previously described HAdV-C5, because it is filtered out by tissue macrophages to a lesser extent. HAdV-C6 has a 10-fold lower LD50 in hamsters than HAdV-C5 and the pathology is caused by virus replication to a larger extent. We show that valganciclovir (VGCV), a drug that was shown to be active against intravenous HAdV-C5 infection previously, is efficacious against HAdV-C6 when administered either prophylactically or therapeutically. Further, we show for the first time that VGCV, and to a lesser extent CDV, can be used to treat respiratory adenovirus infections in the hamster model. These results extend the utility of the hamster model, and demonstrate the efficacy of two drugs available for clinicians to treat adenovirus infections. MDPI 2017-06-13 /pmc/articles/PMC5490823/ /pubmed/28608847 http://dx.doi.org/10.3390/v9060147 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Toth, Karoly
Spencer, Jacqueline F.
Ying, Baoling
Tollefson, Ann E.
Wold, William S. M.
HAdV-C6 Is a More Relevant Challenge Virus than HAdV-C5 for Testing Antiviral Drugs with the Immunosuppressed Syrian Hamster Model
title HAdV-C6 Is a More Relevant Challenge Virus than HAdV-C5 for Testing Antiviral Drugs with the Immunosuppressed Syrian Hamster Model
title_full HAdV-C6 Is a More Relevant Challenge Virus than HAdV-C5 for Testing Antiviral Drugs with the Immunosuppressed Syrian Hamster Model
title_fullStr HAdV-C6 Is a More Relevant Challenge Virus than HAdV-C5 for Testing Antiviral Drugs with the Immunosuppressed Syrian Hamster Model
title_full_unstemmed HAdV-C6 Is a More Relevant Challenge Virus than HAdV-C5 for Testing Antiviral Drugs with the Immunosuppressed Syrian Hamster Model
title_short HAdV-C6 Is a More Relevant Challenge Virus than HAdV-C5 for Testing Antiviral Drugs with the Immunosuppressed Syrian Hamster Model
title_sort hadv-c6 is a more relevant challenge virus than hadv-c5 for testing antiviral drugs with the immunosuppressed syrian hamster model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490823/
https://www.ncbi.nlm.nih.gov/pubmed/28608847
http://dx.doi.org/10.3390/v9060147
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