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 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.
['Toth|Karoly|K|', 'Spencer|Jacqueline F|JF|', 'Ying|Baoling|B|', 'Tollefson|Ann E|AE|', 'Wold|William S M|WSM|']
D000072283:A549 Cells D000257:Adenoviridae Infections D000258:Adenovirus Infections, Human D000260:Adenoviruses, Human D000818:Animals D000998:Antiviral Agents D002460:Cell Line D000077404:Cidofovir D006224:Cricetinae D003596:Cytosine D004195:Disease Models, Animal D015774:Ganciclovir D006801:Humans D007165:Immunosuppression Therapy D008099:Liver D008297:Male D063065:Organophosphonates D000077562:Valganciclovir D019562:Viral Load D014779:Virus Replication
antiviral hamster adenovirus animal model