Blood mononuclear cells from 47 cats experimentally infected with feline immunodeficiency virus (FIV) were examined by using monoclonal antibodies directed against feline CD4 and CD8 homologs, a panT cell antigen, and cell surface immunoglobulin. Significant inversion of the CD4+/CD8+ T-cell ratio was observed only in cats that were infected for 18 months or more. This inversion was associated with a decrease in the absolute numbers of CD4+ T cells and a concomitant increase in CD8+ cells. However, the total numbers of circulating T and B cells were not significantly reduced. Cats infected with FIV for 24 to 28 months also had significantly elevated levels of serum immunoglobulin G (IgG), but normal levels of IgA and IgM. The long-term decline in CD4+ T cells and hypergammaglobulinemia observed in FIV-infected cats resemble the abnormalities occurring in humans after human immunodeficiency virus infection.
Infection of domestic cats with the feline immunodeficiency virus (FIV) represents an important veterinary health problem and a useful animal model for the development of vaccines against acquired immunodeficiency syndrome (AIDS). Two experimental FIV vaccines have been developed; one consisting of fixed infected cells (Vaccine 1), the other of inactivated whole virus (Vaccine 2). After 4-6 immunizations over 2-5 months, both vaccines induced a strong FIV-specific immune response including neutralizing antibody and T-cell proliferation. Vaccine 1 protected 6 of 9 and Vaccine 2 protected 5 of 6 recipient cats against any detectable infection with a low dose (10 animal ID50) of FIV given intraperitoneally 2 weeks after the final boost. One additional cat in each vaccine group had a transient infection at 5-7 weeks postchallenge following which virus could no longer be detected. Thus, a total of 13 of 15 vaccinated cats were protected against persistent infection. By contrast, 13 of 13 controls were persistently infected by this challenge. The infected cell vaccine failed to protect against a higher dose (5 x 10(4) ID50) of FIV. These results indicate that vaccine prophylaxis against natural FIV infection should be achievable and enhance optimism of the prospect of developing an effective AIDS vaccine for humans.
Two interleukin 2 (IL-2)-independent feline immunodeficiency virus (FIV) producer cell lines (FL-4 and FL-6) were produced by selecting cells from an IL-2-dependent culture of mixed peripheral blood lymphocytes infected with FIV. The new cell lines have been stable for over 1 year and spontaneously produce FIV with an average reverse transcriptase titer of 300,000 cpm/ml and an average sucrose gradient purified viral protein concentration of 1 mg/l. FIV produced from these cultures is highly infectious in vitro and in vivo. The FL-6 cell line was phenotyped as expressing the feline CD8 and Pan-T antigens, while the FL-4 cell line expressed the CD4, CD8, and Pan-T antigens. Both cell lines, however, express high levels of viral core and envelope proteins. Paraformaldehyde-inactivated whole virus and similarly inactivated whole-cell virus preparations induced a strong antibody response to core and envelope antigens in immunized cats. The establishment of FIV-producing feline IL-2-independent peripheral blood lymphocyte lines should be valuable for the development of FIV-diagnostic reagents and vaccines and also as a model for human acquired immunodeficiency syndrome vaccine development.
Preexistent feline leukemia virus (FeLV) infection greatly potentiated the severity of the transient primary and chronic secondary stages of feline immunodeficiency virus (FIV) infection. Of 10 FeLV-FIV carrier cats, 5 died of experimentally induced FIV infection, compared with 2 deaths in 10 cats infected only with FeLV and 1 death in 7 cats infected only with FIV. FIV-infected cats with preexistent FeLV infections developed severe depression, anorexia, fever, diarrhea, dehydration, weight loss, and leukopenia 4 to 6 weeks after infection and were moribund within 2 weeks of the onset of signs, whereas cats infected only with FIV developed much milder self-limiting gross and hematologic abnormalities. Pathologic findings in dually infected cats that died were similar to those observed previously in cats dying from uncomplicated primary FIV infection but were much more widespread and severe. Coinfection of asymptomatic FeLV carrier cats with FIV did not increase the levels of FeLV p27 antigen present in their blood over that seen in cats infected with FeLV alone. The amount of proviral FIV DNA was much higher, however, in dually infected cats than in cats infected only with FIV; there was a greater expression of FIV DNA in lymphoid tissues, where the genome was normally detected, and in nonlymphoid tissues, where FIV DNA was not usually found. Dually infected cats that recovered from the primary stage of FIV infection remained more leukopenic than cats infected with FIV or FeLV alone, and their CD4+/CD8+ T-lymphocyte ratios were inverted. One of these cats developed what was considered to be an opportunistic infection. It was concluded, therefore, that a preexistent FeLV infection in some way enhanced the expression and spread of FIV in the body and increased the severity of both the resulting transient primary and chronic secondary stages of FIV infection. This study also demonstrated the usefulness of the FIV model in studying the role of incidental infectious diseases as cofactors for immunodeficiency-causing lentiviruses.
T-cell subsets were studied by fluorescence-activated cell sorter analysis in 57 feline immunodeficiency virus (FIV)-seropositive cats with naturally acquired FIV infection to see whether CD4+-CD8+ alterations were comparable to those observed in human immunodeficiency virus-infected patients. CD4+ values were decreased and CD8+ values were increased. The CD4+/CD8+ ratio was reduced to 1.6, compared with 3.3 in 33 FIV-seronegative control cats. Variance analysis of data showed a significant influence of FIV seropositivity, sex, and spaying of female cats on CD4+ values. CD8+ values were significantly influenced by FIV seropositivity, age, and breed. These findings indicate a similarity between FIV and human immunodeficiency virus infections, as far as alterations of T-cell subsets are concerned. Feline immunodeficiency virus (FIV), first isolated in California (10), is a typical lentivirus that replicates preferably in feline T-lymphoblastoid cells and is structurally similar to human immunodeficiency virus (HIV). Experimental infection of cats induces transient fever, neutropenia, and lymphadenopathy. Following recovery from the initial phase, cats become lifelong carriers of the virus. One year or more after natural infection, cats may develop a terminal AIDS-like phase (12). Hematologic manifestations of FIV infection, including anemia, lymphopenia, neutropenia, and thrombocytopenia, as well as hyperplasia of individual cell lineages and dysmorphic features in bone marrow, are also similar to those in HIV-seropositive humans (14). Strong similarities between FIV infection and the human AIDS complex have been shown, not only in virus structure and clinical symptoms but also in epidemiological manifestations (12, 15). The human counterpart, HIV, is known to infect predominantly CD4+ T-helper lymphocytes and cells of the monocyte-macrophage lineage (3, 8; for a review, see reference 13). Gradual reduction in both the percentage and the absolute number of CD4+ T cells is one of the most striking immunological consequences of HIV infection. Recently, monoclonal antibodies (MAb) against cat CD4 (1) and CD8 (7) homologs have been developed. We have examined peripheral blood lymphocytes from FIV-positive domestic cats with naturally acquired infection (as judged by seroconversion) by using these anti-CD4 and anti-CD8 MAb. We found a variable reduction of CD4+ lymphocytes and an increased proportion of CD8+ lymphocytes in these cats, as already described in a brief report on 20 FIV-seropositive cats (5). MATERIALS AND METHODS Animals. Fifty-seven domestic cats found to be spontane
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