Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Feline leukemia virus-induced immunodeficiency syndrome in cats as a model for evaluation of antiretroviral therapy. 254 Jan 9

We describe the identification, experimental transmission, and pathogenesis of a naturally occurring powerfully immunosuppressive isolate of feline leukemia virus (designated here as FeLV-FAIDS) which induces fatal acquired immunodeficiency syndrome (AIDS) in 100% (25 of 25) of persistently viremic experimentally infected specific pathogen-free (SPF) cats after predictable survival periods ranging from less than 3 months (acute immunodeficiency syndrome) to greater than one year (chronic immunodeficiency syndrome), depending on the age of the cat at time of virus exposure. The pathogenesis of FeLV-FAIDS-induced feline immunodeficiency disease is characterized by: a prodromal period of largely asymptomatic viremia; progressive weight loss, lymphoid hyperplasia associated with viral replication in lymphoid follicles, lymphoid depletion associated with extinction of viral replication in lymphoid follicles, intractable diarrhea associated with necrosis of intestinal crypt epithelium, lymphopenia, suppressed lymphocyte blastogenesis, impaired cutaneous allograft rejection, hypogammaglobulinemia, and opportunistic infections such as bacterial respiratory disease and necrotizing stomatitis. The clinical onset of immunodeficiency syndrome correlates with the replication of a specific FeLV-FAIDS viral variant, detected principally as unintegrated viral DNA, in bone marrow, lymphoid tissues, and intestine. Two of seven cats with chronic immunodeficiency disease that survived greater than 1 year after inoculation developed lymphoma affecting the marrow, intestine, spleen, and mesenteric nodes. Experimentally induced feline immunodeficiency syndrome, therefore, is a rapid and consistent in vivo model for prospective studies of the viral genetic determinants, pathogenesis, prevention, and therapy of retrovirus-induced immunodeficiency disease.
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PMID:Experimental transmission and pathogenesis of immunodeficiency syndrome in cats. 282 40

Cats exposed to the feline leukemia virus (FeLV) may mount an effective immune response and eliminate the virus, develop a non-viremic, latent infection or become persistently infected and shed the virus. Persistently infected cats commonly die of secondary opportunistic infections that result from FeLV-induced immunosuppression. The acquired immunosuppression is the most frequent and most devastating consequence of FeLV infection in the cat. Immunosuppression is targeted primarily to the cell-mediated immune system and has been attributed to the viral p15e envelope protein. The decreased IgG response and proliferative response to T cell mitogens is thought to be due to a defect in the helper cell function. As a result of T helper cell immunosuppression, infected cats may also have defective cytotoxic lymphocyte and activated macrophage functions which are regulated by their lymphokines. Research has shown that the virus causes a general suppression in the production of T cell-derived lymphokines, including gamma interferon and interleukin 2. A decrease in the function of polymorphonuclear leukocytes has also been reported and may contribute to deaths due to opportunistic infections in FeLV-positive cats. There are numerous parallels between the acquired immunodeficiency syndrome (AIDS) in man and the FeLV-induced immunodeficiency syndrome in cats. Frequent deaths due to opportunistic infections, lymphopenia, depressed cell-mediated immune responses to T cell-dependent antigens despite hypergammaglobulinemia and the presence of a long period of time between infection and the onset of clinical signs are just a few of the syndromes that are similar between the 2 retroviral diseases. A new strain of FeLV, FeLV-FAIDS has been associated with a naturally occurring immunosuppressive syndrome that is strikingly similar to AIDS in man. In addition, a T-lymphotropic retrovirus has recently been identified from cats with an immunodeficiency-like syndrome; this feline lentivirus disease is morphologically similar, but antigenically distinct from the human immunodeficiency virus, the cause of AIDS. Treatment for FeLV immunosuppression is primarily supportive. The development of a soluble tumor cell antigen vaccine has been shown to be efficacious in preventing FeLV infections.
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PMID:Clinical and immunologic aspects of FeLV-induced immunosuppression. 284 93