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J. Virol. doi:10.1128/JVI.00423-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

RABBITPOX AND VACCINIA VIRUS INFECTION OF RABBITS AS A MODEL FOR HUMAN SMALLPOX

Department of Molecular Genetics and Microbiology, Box 100266, 1600 SW Archer Road, ARB R2-231, University of Florida College of Medicine, Gainesville, FL 32610-0266

^* To whom correspondence should be addressed. Email: rmoyer{at}ufl.edu.

	Abstract

The threat of smallpox release and use as a bioweapon has encouraged the search for new vaccines and antiviral drugs as well as development of new small animal models in which their efficacy can be determined. Here we reinvestigate a rabbit model where the intradermal infection of rabbits with very low doses of either rabbitpox virus (RPV) or vaccinia virus Western Reserve (VV-WR) recapitulates many of the clinical features of human smallpox. Following intradermal inoculation with RPV, rabbits develop systemic disease characterized by extensive viremia, numerous secondary lesions on the skin and mucocutaneous tissues, severe respiratory disease, death by 9 days post infection and importantly, natural aerosol transmission between animals. Contrary to previous reports, intradermal infection with VV-WR also resulted in a very similar lethal systemic disease in rabbits, again with natural aerosol transmission between animals. When sentinel and index animals were co-housed, transmission rates approached 100% with either virus with sentinel animals exhibiting a similar, severe disease. Lower rates of transmission were observed when index and sentinel animals were housed in separate cages. Sentinel animals infected with RPV with one exception succumbed to the disease. However, the majority of VV-WR-infected sentinel animals, while becoming seriously ill, survived. Finally, we tested the efficacy of the drug 1-O-hexadecyloxypropyl-cidofovir (HDP-CDV) in the RPV/rabbit model and found that an oral dose of 5 mg/kg BID for 5 days beginning 1 day before infection was able to completely protect rabbits from lethal disease.