Research is directed at determining mechanisms of disease caused by selected human pathogens using experimental animal models of infection. Development of various strains of human pathogens with the aid of recombinant DNA biotechnology provide a means to compare defined pathogen interactions with host animals under controlled experimental conditions to provide clues concerning variations in pathogenesis caused by microorganisms with defined genetic differences. Studies have made use of laboratory rabbits as a model animal. Current investigations emphasize the human retrovirus HTLV-I which causes a spectrum of disease in infected humans or, in some cases, asymptomatic infection. A series of molecular clones of HTLV-I have been prepared. These clones vary by one or two nucleotide substitutions and have been characterized for their in vitro activity. Animals infected by inoculation with cells transfected with the molecular clones or by injection of naked viral DNA are followed and monitored for infection and for disease signs. A recent study found that a high proportion of HTLV-I infected rabbits produced autoantibodies directed against keratin and thyroglobulin. This finding provides a possible mechanism by which infection with this retrovirus may cause certain of the chronic arthritic conditions ascribed to it. Demonstration that animals infected by DNA injection as well as those given infected cell lines supported the notion that the virus was the causative agent rather than reaction to cellular antigens. Another study showed that a variety of disease signs including chronic cutaneous disease, neurologic disorders and aggressive acute leukemia may result in infected animals with little or no change in virus structure. Overall the results indicate that rabbits are susceptible to the spectrum of diseases seen in humans and can provide an excellent model for the study of HTLV-I disease and means to combat it. Work continues on the immune-related genes in the rabbit in an effort to improve the utility of this disease model. Studies of the MHC have yielded a quick method to type outbred rabbits and this testing uncovered a novel allele in the DQA locus.
| Kindt, T J; Said, W A; Bowers, F S et al. (2000) Passage of human T-cell leukemia virus type-1 during progression to cutaneous T-cell lymphoma results in myelopathic disease in an HTLV-1 infection model. Microbes Infect 2:1139-46 |
| Mahana, W; Samaan, A; Zhao, T M et al. (2000) Evidence for humoral and cellular reactivity against keratin and thyroglobulin in HTLV-I infected rabbits. Autoimmunity 32:57-65 |
