Affiliation:
1. Department of Molecular Genetics and Microbiology, Box 100266, 1600 SW Archer Road, ARB R2-231, University of Florida College of Medicine, Gainesville, Florida 32610-0266
Abstract
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 in which 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 postinfection, 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 cohoused, 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 in the RPV/rabbit model and found that an oral dose of 5 mg/kg twice a day for 5 days beginning 1 day before infection was able to completely protect rabbits from lethal disease.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference27 articles.
1. Aldern, K. A., S. L. Ciesla, K. L. Winegarden, and K. Y. Hostetler. 2003. Increased antiviral activity of 1-O-hexadecyloxypropyl-[2-C-14] cidofovir in MRC-5 human lung fibroblasts is explained by unique cellular uptake and metabolism. Mol. Pharm.63:678-681.
2. Bedson, H. S., and M. J. Duckworth. 1963. Rabbit pox: an experimental study of the pathways of infection in rabbits. J. Pathol. Bacteriol.85:1-20.
3. Ciesla, S. L., J. Trahan, W. B. Wan, J. R. Beadle, K. A. Aldern, G. R. Painter, and K. Y. Hostetler. 2003. Esterification of cidofovir with alkoxyalkanols increases oral bioavailability and diminishes drug accumulation in kidney. Antivir. Res.59:163-171.
4. Condit, R. C., and A. Muzyczka. 1981. Isolation and preliminary characterization of temperature-sensitive mutants of vaccinia virus. Virology113:224-241.
5. Esposito, J., and F. Fenner. 2001. Poxviruses, p. 2885-2922. In D. E. Knipe and P. M. Howley (ed.), Fields virology. Lippincott Williams & Wilkins, Philadelphia, PA.
Cited by
58 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献