didanosine and Immunologic-Deficiency-Syndromes

The SCID-hu mouse is a small animal in which human hematolymphoid organs can be engrafted and maintained in vivo. In this study, parameters are described for reproducible infection of SCID-hu mice after i.v. inoculation. Infection was found to be dependent upon the time after inoculation, the virus isolate, the titer of virus, and the human target organ implanted into the mouse. Ten to 14 days after the i.v. administration of HIV isolates derived freshly from patients (e.g., JR-CSF, JR-FL, SM), 100% of engrafted human lymph nodes in SCID-hu mice were infected; greater than 95% of these animals were also viremic. Implants of human thymus or connective tissue, as well as the endogenous murine hematolymphoid organs, were not infected. As demonstrated by a combination of in situ hybridization and immunohistochemistry, both T-lymphoid and myelomonocytic lineage cells were infected in this system. HIV isolates that have been adapted to growth in vitro (e.g., HTLV-IIIb) were not infectious. When either 3'-azido-3'-deoxythymidine (AZT) or 2',3'-dideoxyinosine (ddIno) was administered to SCID-hu mice before HIV infection, the animals were protected in dose ranges similar to those used in man. This animal model may now be used as an efficient intermediate step between the lab and the clinic to study the infectious process in vivo and to best select efficacious antiviral compounds against HIV.

Topics: Animals; Antiviral Agents; Didanosine; DNA, Viral; HIV; HIV Infections; Humans; Immunohistochemistry; Immunologic Deficiency Syndromes; Lymph Nodes; Macrophages; Mice; Nucleic Acid Hybridization; Polymerase Chain Reaction; T-Lymphocytes; Transplantation, Heterologous; Zidovudine

In the present communication we evaluate the feline leukemia virus (FeLV) infection of cats as a model for antiretroviral chemotherapy studies. Additionally, we report the results of testing the antiviral effect of the compounds, 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxycytidine, 2',3'-dideoxyinosine and 2',3'-dideoxyadenosine against FeLV replication in vitro. Cumulative data from experiments in which FeLV-infected cats were treated with AZT at different stages of experimental infection are also evaluated.

Topics: Acquired Immunodeficiency Syndrome; Animals; Antibodies, Viral; Antiviral Agents; Cats; Cell Line; Didanosine; Dideoxyadenosine; Dideoxynucleosides; Disease Models, Animal; Drug Evaluation, Preclinical; Immunologic Deficiency Syndromes; Leukemia Virus, Feline; Leukemia, Experimental; Nucleosides; Specific Pathogen-Free Organisms; Virus Replication; Zalcitabine; Zidovudine