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Viruses 2015, 7(3), 1409-1428; doi:10.3390/v7031409

Valganciclovir Inhibits Human Adenovirus Replication and Pathology in Permissive Immunosuppressed Female and Male Syrian Hamsters

1
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, MO 63104, USA
2
Department of Biology, Indiana University ­ Purdue University Indianapolis, Indianapolis, IN 46202, USA
3
Department of Comparative Medicine, Saint Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, MO 63104, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 20 January 2015 / Revised: 10 March 2015 / Accepted: 16 March 2015 / Published: 23 March 2015
(This article belongs to the Section Antivirals & Vaccines)
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Abstract

Adenovirus infections of immunocompromised pediatric hematopoietic stem cell transplant patients can develop into serious and often deadly multi-organ disease. There are no drugs approved for adenovirus infections. Cidofovir (an analog of 2-deoxycytidine monophosphate) is used at times but it can be nephrotoxic and its efficacy has not been proven in clinical trials. Brincidofovir, a promising lipid-linked derivative of cidofovir, is in clinical trials. Ganciclovir, an analog of 2-deoxyguanosine, has been employed occasionally but with unknown efficacy in the clinic. In this study, we evaluated valganciclovir against disseminated adenovirus type 5 (Ad5) infection in our permissive immunosuppressed Syrian hamster model. We administered valganciclovir prophylactically, beginning 12 h pre-infection or therapeutically starting at Day 1, 2, 3, or 4 post-infection. Valganciclovir significantly increased survival, reduced viral replication in the liver, and mitigated the pathology associated with Ad5 infection. In cultured cells, valganciclovir inhibited Ad5 DNA replication and blocked the transition from early to late stage of infection. Valganciclovir directly inhibited Ad5 DNA polymerase in vitro, which may explain, at least in part, its mechanism of action. Ganciclovir and valganciclovir are approved to treat infections by certain herpesviruses. Our results support the use of valganciclovir to treat disseminated adenovirus infections in immunosuppressed patients. View Full-Text
Keywords: adenovirus; antiviral; hamster; valganciclovir adenovirus; antiviral; hamster; valganciclovir
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MDPI and ACS Style

Toth, K.; Ying, B.; Tollefson, A.E.; Spencer, J.F.; Balakrishnan, L.; Sagartz, J.E.; Buller, R.M.L.; Wold, W.S.M. Valganciclovir Inhibits Human Adenovirus Replication and Pathology in Permissive Immunosuppressed Female and Male Syrian Hamsters. Viruses 2015, 7, 1409-1428.

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