The feline acquired immune deficiency syndrome (FAIDS), induced in cats by experimental infection with feline leukemia virus (FeLV), will be used as an animal model of AIDS to study retrovirus-associated immune suppression. Initial studies will utilize dosages of a conventional strain of FeLV to induce a higher incidence of immunosuppression than leukemia. The clinical, immunological and pathological manifestations of FAIDS will be documented, followed by in-depth study of the mechanisms responsible for immunosuppression as follows: a) changes in lymphocyte subpopulations will be quantitated using monoclonal antibodies developed against these cells; b) these changes will be correlated with functional changes in the ability of these cells to mediate help or suppression in vitro; c) virus receptors will be quantitated using anti-idiotype antibodies developed against existing anti-FeLV monoclonal antibodies; d) the response to, and production of T-cell growth factor (TCGF or IL-2) will be assayed; e) the influence of FeLV on macrophage function in vitro will be studied by measuring IL-1 and prostaglandin (PG) production, and the effect of indomethacin, a PG inhibitor. A second major emphasis of the proposed work is to identify FeLV variants which selectively produce FAIDS. This variant will be sought amongst a) existing molecular clones of FeLV, or will be newly cloned from b) conventional strains of FeLV with both immunosuppressive and leukemic properties, c) isolation of """"""""helper"""""""" leukemia virus from inoculums of feline sarcoma virus, or d) FeLV isolated from naturally occurring cases of FAIDS. The genome and gene products of FAIDS-selective variants of FeLV will be characterized and compared to that of known conventional strains of FeLV. The mechanism of immunosuppression by FAIDS-selective variants will also be studied according to the same procedures described above for conventional FeLV.
| Tavares, L; Roneker, C; Postie, L et al. (1989) Testing of nucleoside analogues in cats infected with feline leukemia virus: a model. Intervirology 30 Suppl 1:26-35 |
| Tavares, L; Roneker, C; Johnston, K et al. (1987) 3'-Azido-3'-deoxythymidine in feline leukemia virus-infected cats: a model for therapy and prophylaxis of AIDS. Cancer Res 47:3190-4 |
