Comparative biological responses of rabbits infected with human T-lymphotropic virus type I isolates from patients with lymphoproliferative and neurodegenerative disease

Abstract

An experimental rabbit model was used to determine host responses to infection by various human T-lymphotropic virus type-I (HTLV-I) strains. Seven groups of 4 to 5 rabbits each were inoculated with lethally-irradiated HTLV-I-infected cell lines derived from patients with adult T-cell leukemia/lymphoma or from patients with HTLV-I-associated myelopathy. Four separate control groups of 2 rabbits each were inoculated with similarly prepared HTLV-I-negative cells derived from rabbits or humans. Anti-viral antibody responses were assessed by immunoblot assay and hematologic parameters were measured using automated cell counters and cytologic staining. The virologic status of challenged rabbits was determined by co-culture and HTLV-I antigen capture assay, as well as by polymerase chain reaction (PCR) amplification of HTLV-I DNA from peripheral blood mononuclear cells (PBMC) or tissues. The HTLV-I inocula could be separated into groups based upon their infectivity to rabbits: highly infectious strains elicited intense serologic responses and were detected frequently in tissues by antigen and PCR assays, while other strains were moderately to poorly infectious, induced weak antibody responses and were infrequently detected by antigen and PCR assays. Overall, PBMC appeared to have the greatest quantity of HTLV-I containing cells, while bone marrow was a poor source of virus. No clinical or hematologic abnormalities were evident during the 24-week course of infection. Taken together, our results suggest there is heterogeneity in the biological response to HTLV-I infection which is, in part, dependent on the infecting strain of virus.