A cat experimentally infected with feline immunodeficiency virus (FIV) but known to be free of feline leukaemia virus (FeLV) developed lymphosarcoma. The lesions in the liver and kidneys were present nine months after infection, when the cat was 21 months old. The cat had no overt signs of immunodeficiency and it is suggested that the B cell activation induced shortly after FIV infection produced a large pool of proliferating lymphocytes from which the malignant cells emerged.
The role of cellular immunity in the establishment and progression of immunosuppressive lentivirus infection remains equivocal. To develop a model system with which these aspects of the host immune response can be studied experimentally, we examined the responses of cats to a hybrid peptide containing predicted Tand B-cell epitopes from the gag and env genes of feline immunodeficiency virus (FIV). Cats were immunized with an unmodified 17-residue peptide incorporating residues 196 to 208 (from gag capsid protein p24) and 395 to 398 (from env glycoprotein gp120) of the FIV Glasgow-8 strain by using Quil A as an adjuvant. Virus-specific lymphocytotoxicity was measured by chromium-51 release assays. The target cells were autologous or allogeneic skin fibroblasts either infected with recombinant FIV gag vaccinia virus or pulsed with FIV peptides. Effector cells were either fresh peripheral blood mononuclear cells or T-cell lines stimulated with FIV peptides in vitro. Cytotoxic effector cells from immunized cats lysed autologous, but not allogeneic, target cells when they were either infected with recombinant FIV gag vaccinia virus or pulsed with synthetic peptides comprising residues 196 to 205 or 200 to 208 plus 395. Depletion of CD8+ T cells, but not CD4+ T cells, from the effector cell population abrogated the lymphocytotoxicity. Immunized cats developed an antibody response to the 17-residue peptide immunogen and to recombinant p24. However, no antibodies which recognized smaller constituent peptides could be detected. This response correlated with peptide-induced T-cell proliferation in vitro. This study demonstrates that cytotoxic T lymphocytes specific for FIV can be induced following immunization with an unmodified short synthetic peptide and defines a system in which the protective or pathological role of such responses can be examined.
Direct inoculation of genetic material in DNA form is a novel approach to vaccination that has proved efficacious for a number of viral agents. We are interested in the potential of this approach for the delivery of vaccines based on attenuated or replication-defective retroviruses. Toward this goal, we tested the effect of intramuscular inoculation of a plasmid containing the entire genome of feline immunodeficiency virus (FIV-Petaluma, F14 clone). DNA delivery was compared with intramuscular or intraperitoneal inoculation of virus reconstituted from the same molecular clone. The outcome was monitored by serological analysis and quantitative virus load determination over a 31-week period. DNA inoculation was found to be a reliable means of infection, although seroconversion and the rise in PBMC virus load were delayed relative to intramuscular or intraperitoneal inoculation of virus. At 31 weeks, similar levels of proviral DNA were detected in central lymphoid tissue of all infected animals. In conclusion, DNA inoculation of proviral DNA will be of use as a novel method of cell-free virus challenge and may have further potential for the delivery of lentiviral vaccines.
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