Severe progressive immunodeficiency syndrome can be induced experimentally with a molecularly cloned isolate of feline leukemia virus (FeLV-
FAIDS). The resultant disease syndrome is characterized by persistent
viremia,
lymphopenia, progressive
weight loss, persistent
diarrhea, enteropathy, and
opportunistic infections. The onset of clinical immunodeficiency disease is prefigured by the replication of the FeLV-
FAIDS variant virus in bone marrow and other tissues. The FeLV-
FAIDS system can be used to evaluate
antiviral agents which act on steps in the replication cycle which are conserved among retroviruses (e.g.
reverse transcriptase,
protease, assembly). The persistence and magnitude of
viremia serves as a useful parameter in
antiviral studies because it can be easily measured, presages the eventual development of immunodeficiency, and provides a convenient
indicator of therapeutic efficacy either in preventing de novo FeLV
infection or in reversing or ameliorating established
infection. We describe here the evaluation of
2',3'-dideoxycytidine (ddC) against FeLV-
FAIDS infection - both in vitro in cell culture assay systems and in vivo in cats administered ddC either via intravenous bolus dosage or via controlled release subcutaneous implants. We found that, although controlled release delivery of ddC inhibited de novo FeLV-
FAIDS replication and delayed onset of
viremia when
therapy was discontinued (after 3 weeks), an equivalent incidence and level of
viremia were established rapidly in both ddC-treated and control cats. The FeLV model, therefore, can be used to assess rapidly experimental single agent or combined
antiviral therapies for persistent
retrovirus infection and disease.