Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Feline leukemia viruses (FeLVs) belonging to interference subgroup C induce fatal anemia resembling human pure red cell aplasia (PRCA). Subgroup A FeLVs, although closely related genetically to FeLVs of subgroup C, do not induce PRCA. The determinants for PRCA induction by a molecularly cloned prototype subgroup C virus (FeLV-Sarma-C [FSC]) have been localized to the N-terminal 241 amino acids of the surface glycoprotein (SU) gp70. To investigate whether the anemogenic activity of FSC reflects a unique capacity to infect erythroid progenitor cells, we used correlative immunogold, immunofluorescence, and cytological staining to study prospectively the hemopoietic cell populations infected by either FSC or FeLV-FAIDS-61E-A (F6A), a prototype of subgroup A virus. The results demonstrated that although only FSC-infected animals developed erythrocyte aplasia, the env SU and the major core protein (p27) were expressed in a surprisingly large fraction of the lymphoid, erythroid, and myeloid lineage marrow cells in both FSC- and F6A-infected cats. Between days 8 and 17 postinoculation, gp70 and p27 were detected in 43 to 73% of erythroid, 25 to 75% of lymphoid, and 35 to 50% of myeloid lineage cells, regardless of whether the cats were infected with FSC or F6A. Thus, anemogenic subgroup C and nonanemogenic subgroup A FeLVs have similar hemopoietic cell tropism and infection kinetics, despite their divergent effects on erythroid progenitor cell function. Acute anemia induction by subgroup C FeLV, therefore, does not reflect a unique tropism for marrow erythroid cells but rather indicates a unique cytopathic effect of the SU on erythroid progenitor cells.
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PMID:Hematopoietic target cells of anemogenic subgroup C versus nonanemogenic subgroup A feline leukemia virus. 132 10

Cats infected with molecularly cloned FeLV-FAIDS develop an immunodeficiency syndrome characterized by persistent antigenemia, decline in circulating CD4+ T lymphocytes, and impaired T-cell-dependent immune responses and opportunistic infection. We evaluated the capacity of PMEA to inhibit the replication of FeLV-FAIDS in vitro and to inhibit the progression of FeLV-FAIDS infection in vivo. We found that PMEA inhibited replication of FeLV-FAIDS by greater than or equal to 50% at concentrations of greater than or equal to 0.5 microgram/ml (1.63 microM) in feline fibroblasts and prevented T lymphocyte killing at concentrations of 3 micrograms/ml. PMEA administered to cats at dosages of greater than or equal to 6.25 mg/kg/day from 0 to 49 days after FeLV-FAIDS infection prevented the development of persistent antigenemia and the induction of immunodeficiency disease. In contrast to placebo treated controls, cats successfully treated with PMEA contained viral infection, developed neutralizing antibody, and resisted a second virulent virus challenge without further therapy. Manifestations of PMEA toxicity produced by higher dosages (25 or 12.5 mg/kg/day) were anemia, leukopenia, and diarrhea. These results indicate PMEA to be a potent antiretroviral agent effective in aborting fatal progression of FeLV-FAIDS infection when therapy is initiated at the time of virus exposure.
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PMID:Early therapy of feline leukemia virus infection (FeLV-FAIDS) with 9-(2-phosphonylmethoxyethyl)adenine (PMEA). 166 30

Friend virus clearly provides an important model for understanding the molecular biology of cancer. Moreover, the most important aspects of the erythroleukemia can be caused by a single SFFV infection in the absence of any helper virus. The SFFV env gene encodes a membrane glycoprotein, gp55. This glycoprotein, when expressed on erythroblast surfaces, causes a constitutive mitogenesis. However, SFFV infections only rarely increase the cell's self-renewal capability or abrogate its commitment to differentiate. Therefore, the consequence of infection is initially a polyclonal erythroblastosis. This polyclonal proliferation usually leads to cell differentiation and to recovery unless helper virus is present to cause continuing infection of new erythroblasts. Extremely rare SFFV proviral integrations, however, result in abrogation of the cell's commitment to differentiate and in the concomitant acquisition of cell immortality. These immortalizing proviral integrations occur at only a small number of sites in the mouse genome. Therefore, the mitogenic and immortalizing stages of erythroleukemia are now known to be caused by discrete genetic events--the first involving the SFFV env gene and the second involving the rare proviral integration sites. In early investigations of Friend virus, the first stage always preceded the second stage by at least several weeks. Now it is known that this delay in onset of the second stage is caused solely by statistics. Every SFFV-infected erythroblast is mitogenically activated, yet only rarely does the SFFV proviral integration produce immortality. Both steps in leukemogenesis can be caused simultaneously in an erythroblast by a rare single SFFV proviral integration. There has been an explosion of interest in retroviral env gene-mediated pathogenesis. Such pathogenesis has been recently associated with most of the naturally transmitted retroviral diseases including AIDS. Such pathogenesis involves in different viruses immunosuppression, anemia, neuropathy, and leukemia (Mathes et al. 1978; Simon et al. 1984, 1987; Weiss et al. 1985; Lifson et al. 1986; Riedel et al. 1986; Sitbon et al. 1986; Sodroski et al. 1986; Mitani et al. 1987; Schmidt et al. 1987; Klase et al. 1988; Overbaugh et al. 1988a, b). The shuffling and dynamic env gene rearrangements that have been associated with murine retroviral leukemogenesis have also now been seen in FeLV-FAIDS and HIV (Fisher et al. 1988; Overbaugh et al. 1 t88b; Saag et al. 1988; Tersmette et al. 1988). Friend virus provides an important established example of such env gene pathogenesis. Although we still do not understand precisely how gp55 causes erythroblast mitosis, workers in this field have discovered important clues that may lead to answers.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Molecular biology of Friend viral erythroleukemia. 268 47

Feline leukaemia viruses (FeLVs) have long been known to be associated with induction of proliferative and anti-proliferative diseases of domestic cats. Strains of FeLV have been recognized which specifically induce lymphosarcoma, aplastic anaemia, myelodysplastic anaemia, and, recently, feline AIDS (acquired immune deficiency syndrome), a naturally occurring immunosuppressive syndrome strikingly similar to human AIDS which is lethal in 100% of inoculated and viraemic specific-pathogen-free (SPF) cats. Here, we have analysed FeLV DNA in tissues of 22 SPF cats that had been inoculated with the feline AIDS strain (FeLV-FAIDS) and we find two classes of viral DNA--a monotypic common form which is detectable in bone marrow regardless of disease state, and variant forms, recognizable by restriction site differences, whose appearance correlates with onset of disease symptoms and persists throughout the course of the disease. FeLV-FAIDS variant DNA is detected at high concentration (10-50 copies per cell) and principally as unintegrated viral DNA (UVD) in bone marrow of cats with feline AIDS. In marked contrast high levels of UVD were not present in cats in the terminal-stages of T-cell lymphosarcoma, aplastic anaemia, or myelodysplastic anaemia induced by other FeLV strains. These results parallel recent observations in humans, where high levels of UVD were sometimes found in cells derived from AIDS patients infected with human T-lymphotropic virus type III (HTLV-III)/lymph-adenopathy-associated virus (LAV), and suggest that persistence of unintegrated variant viral DNA is a crucial indicator of retrovirus-induced cytopathic disease syndromes such as AIDS.
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PMID:Disease-specific and tissue-specific production of unintegrated feline leukaemia virus variant DNA in feline AIDS. 300 39