Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemotactic responsiveness of mononuclear phagocytes has often been found defective in patients with various malignancies. We have previously reported a defective chemotactic responsiveness in patients with head and neck cancer. Low-molecular-weight factors (LMWFs) have been isolated from tumors and can be held responsible for the inhibitory effect on monocyte chemotactic responsiveness. It is an intriguing new finding that these LMWFs can be neutralized by antibodies reactive to P15E, a structural envelope protein of murine leukemia retroviruses. In this report we describe a relatively easy and rapid method for the detection of immunosuppressive P15E-like factors in the sera of patients with head and neck cancer. The test is based on the monocyte polarization assay. Although only nine head and neck cancer patients were included in this study, the findings indicate that the test might be of value for clinical application. An early detection of a recurrence after treatment might be possible by the finding of a reappearance of the P15E-like factors in patients' sera during follow-up.
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PMID:Immunosuppressive retroviral-related factors in sera of patients with head and neck cancer. 227 7

CD4 molecules on human cells function as a major receptor for human immunodeficiency virus (HIV); however, certain CD4-negative cell types may also be susceptible to infection. Therefore, we attempted to quantitate the relationship between HIV infection and CD4 expression on human cell lines before and after introduction of the CD4 gene by using a retrovirus vector. Prior to introduction of the CD4 expression vector, low levels of HIV infection were detected by a sensitive focal immunoassay on all three cell types studied. With several HIV strains in clones of human cervical carcinoma (HeLa) cells expressing different levels of CD4, HIV titer increased with increasing CD4 expression. In contrast, in squamous cell carcinoma cells (SCL1) and astroglial cells (U87MG), even high levels of CD4 expression failed to augment HIV infection. The CD4 protein expressed in these two cell lines had the expected molecular weight and was capable of binding HIV virions. However, in contrast to CD4-positive HeLa cells, CD4-positive U87MG and SCL1 cells were unable to form syncytia when cultured with cells expressing HIV envelope protein. Thus, the inability of HIV to infect these cells appeared to be due to lack of fusion between HIV virion envelope proteins and CD4-positive cell membranes. This block is infectivity was overcome when cells were infected with HIV which was pseudotyped with the envelope protein of amphotropic murine leukemia virus. Thus, in addition to CD4, other cell surface molecules appear to be required for successful HIV entry into and infection of these two human cell lines.
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PMID:Failure of human immunodeficiency virus entry and infection in CD4-positive human brain and skin cells. 229 63

Mouse monoclonal antibodies directed against different epitopes of the murine leukemia virus envelope protein gp70 were used to study the expression of retroviral related env proteins during mouse oocyte maturation, fertilization and blastocyst formation. A gp70-related antigen was detected with immunohistochemistry in growing oocytes but not in primordial and primary non-growing oocytes. Atretic oocytes were also negative. Both parthenogenetically activated and fertilized oocytes were positive. Two-cell stages showed a patchy distribution of the antigen. Later preimplantation stages were negative except for a markedly positive period during compaction of the morula and adhesion of the blastocyst.
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PMID:A retroviral gp70-related protein is expressed at specific stages during mouse oocyte maturation and in preimplantation embryos. 247 73

The envelope glycoprotein (gp70) of a molecularly cloned, replication-defective feline leukemia virus (FeLV-FAIDS clone 61C) carries determinants for induction of fatal immunodeficiency disease, whereas the gp70 of its companion replication-competent, probably parent virus (clone 61E) does not. Immunoprecipitation analysis of the extracellular glycoproteins of 61E and EECC, a replication-competent viral construct composed of the 61C env and 3' long terminal repeat fused to the 61E gag-pol genes, demonstrated that the gp70 of EECC could be distinguished from that of 61E by both feline immune serum and a murine monoclonal antibody. Molecular weights of both the envelope precursor polyprotein (gp80) and the mature extracellular glycoprotein (gp70) of 61E were smaller than the corresponding proteins from the pathogenic EECC. Both the molecular weight disparity and monoclonal antibody discrimination of the two gp80s were abolished by inhibition of envelope protein glycosylation with tunicamycin, whereas the apparent gp70 size differences were resolved by enzymatic removal of N-linked oligosaccharides. Pulse-chase studies in EECC-infected cells demonstrated that processing of gp80 to gp70 was delayed and that this retardation of envelope glycoprotein processing could be simulated in 61E-infected cells by treatment with the glucosidase inhibitor N-methyldeoxynojirimycin, a compound that causes retention of oligosaccharides in the high-mannose form. The resultant 61E gp70 then could be recognized by sera from EECC-immunized cats. The presence of a higher content of sialic acid on the apathogenic 61E gp70 indicated that oligosaccharides of 61E and EECC gp70 were processed differently. These data suggested that the unique biochemical properties which distinguish the envelope glycoproteins of the FeLV-FAIDS variant from its companion apathogenic parent virus were responsible for T-cell cytopathicity and induction of immunodeficiency disease. Further biochemical characterization of these glycoproteins should be useful in understanding the pathogenic mechanisms of immunodeficiency disease induced by retroviruses.
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PMID:Posttranslational modifications distinguish the envelope glycoprotein of the immunodeficiency disease-inducing feline leukemia virus retrovirus. 253 25

The polycythemia-inducing strain of the Friend spleen focus-forming virus (SFFVP) induces an acute erythroleukemia in mice. Erythroid cells from these mice differ from normal erythroid cells in that they can proliferate and differentiate in the apparent absence of the erythroid hormone erythropoietin (Epo). Although it was recently shown that the unique envelope protein encoded by SFFV is responsible for altering the hormonal requirements of erythroid cells for growth and differentiation, the mechanisms by which this occurs is not known. Since the SFFV envelope protein appears to interact with a target present only in erythroid cells and since Epo is specific for these cells, it is possible that the virus is exerting its effect through this hormone. In an effort to ascertain if this is the case, we examined cells from SFFVP-infected mice to determine (a) if they produce Epo or other erythroid growth factors that stimulate erythroid cells to grow in an autocrine-like manner and (b) if they express elevated numbers of Epo receptors that may result in a reduced requirement for the level of Epo needed for growth and differentiation. Our results indicate that SFFVP-infected cells do not secrete Epo or any other erythroid growth factors that could account for the reduced hormonal requirements of these cells. Also, our studies using iodinated Epo in cell binding assays and cross-linking studies indicate that SFFVP-infected cells are not significantly different from normal erythroid cells in the number, affinity, or size of their Epo receptors.
Leukemia 1989 Oct
PMID:Apparent Epo-independence of erythroid cells infected with the polycythemia-inducing strain of Friend spleen focus-forming virus is not due to Epo production or change in number or affinity of Epo receptors. 255 Jul 8

Fv-4 is a mouse gene which controls susceptibility to infection by ecotropic murine leukemia virus (MuLV). We previously cloned part of an endogenous MuLV associated with the resistance allele of the Fv-4 gene (Fv-4r). In this report, we describe an extended clone of the Fv-4r allele consisting of a 17-kilobase DNA fragment containing the retroviral sequence and its 5'-flanking sequence. The new DNA clone contains a truncated MuLV with delta pol-env-long terminal repeat sequences but no other MuLV-reactive sequence within 13 kilobases upstream of the truncated MuLV. Transfection of this clone into mouse cells led to transcription of Fv-4 env mRNA, expression of the Fv-4r-specific MuLV envelope protein, and resistance to infection with ecotropic MuLV but not amphotropic and dualtropic MuLVs. Restriction of ecotropic viruses appears to occur at or before viral cDNA synthesis. This result is consistent with a model of receptor interference for Fv-4 restriction. Our data also suggest that the 5' non-MuLV sequence is important for biological function, since a DNA clone which lacks most of the 5'-flanking sequence did not efficiently confer the resistance phenotype.
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PMID:Fv-4 resistance gene: a truncated endogenous murine leukemia virus with ecotropic interference properties. 255 65

The primary protein product of the human T-cell leukemia virus type 1 (HTLV-1) env gene, gp61, is cleaved to produce both the exterior (gp46) and the transmembrane (gp21) portions of the HTLV-1 envelope protein. To compare the reactivity with human antibodies of different regions of this gp61 protein, five plasmids (A, B, B1, C, and D) were constructed to express recombinant proteins (RPs) in Escherichia coli. RP-A, RP-B, RP-B1, and RP-C contain amino acid residues 26 to 165, 166 to 229, 166 to 201, and 229 to 308, respectively, of the exterior envelope protein gp46. Serum samples from HTLV-1-seropositive subjects were assayed for reactivity with these RPs by Western immunoblotting. The percentages of positive reactivity with each of the RPs were as follows: 18.9% (23 of 122) for RP-A, 89.6% (112 of 125) for RP-B, 70.2% (85 of 121) for RP-B1, and 92.9% (117 of 126) for RP-C. These results indicate that the C-terminal half of gp46 (RP-B plus RP-C) can detect 97.6% (123 of 126) of positive samples, while the N-terminal half of gp46 (RP-A) can only detect 18.9% of the HTLV-1-positive sera (P less than 0.005). Furthermore, RP-A, -B, and -C, which together span the entire length of gp46 except the first five amino acids at the N terminus and the last four amino acids at the C- terminus, detected 99.2% (125 of 126) of the HTLV-1-positive subjects. In contrast, RP-D, which contains the HTLV-1 transmembrane envelope protein gp21 minus the first amino acid at the N terminus, had a lower rate of antibody reactivity at 73.7% (84 of 114) (P less than 0.005). The difference in seropositive rates for RP-D between HTLV-1 carriers (55.6%) and adult T-cell leukemia patients (85.5%) is statistically significant (P less than 0.01). This study therefore indicates that the C-terminal half of gp46, especially the amino acid sequence from 200 to 308, contains the most reactive epitopes of the HTLV-1 gp61 envelope glycoprotein.
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PMID:Antibody reactivity to different regions of human T-cell leukemia virus type 1 gp61 in infected people. 267 6

Various approaches have been considered for generation of effective and safe vaccines against retroviruses, including HIV, with limited success. In the present vaccination study, encompassing 137 household cats, we have composed an experimental ISCOM subunit vaccine containing gp70 of feline leukaemia virus (FeLV)--the external glycosylated envelope protein, and the transmembrane protein p15E, with a commercial available inactivated FeLV vaccine (Leukocell). The two vaccines were estimated to contain approximately the same amount of gp70 antigen and the cats were immunized three times according to the recommendations of the commercial vaccine. A control preparation not containing gp70 or p15E was also included. During the observation period of 200 days all cats remained healthy and no virus was isolated during the isolation attempts. The serological responses were measured in ELISA, membrane immunofluorescence (MIF) and virus neutralization (VN) tests. In contrast to the cats in the other groups almost all ISCOM-vaccinated cats responded by seroconversion or increased titres in the three tests. The development of specific antibodies to gp70 and p15E were confirmed in Western blot. These results clearly illustrate the potential of the ISCOM structure for the development of safe and effective vaccines against retroviruses.
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PMID:Serological responses in cats vaccinated with FeLV ISCOM and an inactivated FeLV vaccine. 275 Feb 71

Retroviral infections are accompanied by immunosuppression in a variety of species. For feline leukemia virus, the immunosuppression has been ascribed to the transmembrane envelope protein, p15E, which suppresses the proliferative responses of cat, mouse, and human lymphocytes. A similar suppressive effect has been shown for a lysate of human immunodeficiency virus (HIV), strain HTLV-IIIB. Here we determined that detergent-disrupted HTLV-IIIB lystate exerted a strong suppressive effect on PHA-stimulated lymphocytes. Preparations of whole virions, a lysate of a local HIV isolate grown on MP-6 cells, and a commercially obtained UV and psoralene-inactivated lysate were examined and demonstrated to have a similar suppressive effect. The HIV lysate was not directly cytotoxic to lymphocytes and did not contain tumor necrosis factor or lymphotoxin. The HIV lysate specifically suppressed the proliferation of a range of hemopoietic cell lines from man and mouse including three EBV transformed CD4- and IL-2 receptor-negative B-cell lines. The lysate also suppressed the formation of human bone marrow colonies, whereas the lysate had only a slight or no effect on fibroblasts. The suppression of lymphocyte proliferation was not abrogated by addition of IL-2 or IL-1 and the HIV lysate inhibited the expression of IL-2 receptors on suboptimal PHA-stimulated mononuclear cells. The suppressive factor(s) has not been characterized in molecular terms, but suppressive activity was recovered in fractions with a molecular weight of about 67,000 and in both the glycoprotein fraction and in the glycoprotein-depleted fraction of the HIV lysate. Sera from one-third of a small series (N = 13) of individuals with antibodies to HIV seem to be able to neutralize the suppressive properties of HIV lysate in cultures.
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PMID:Investigation of immunosuppressive properties of inactivated human immunodeficiency virus and possible neutralization of this effect by some patient sera. 278 62

Bone marrow fibroblast colony-forming units (CFU-F) were evaluated in cats experimentally infected with feline leukemia virus (FeLV). Cats that developed persistent viral infection and anemia (progressor cats) had a progressive decrease in the number of CFU-F at 2, 4, 6, 8, and 10 weeks after inoculation with FeLV. This suppression of CFU-F number in progressor cats ranged from 16 to 44% of the preinoculation CFU-F value. Cats that did not develop persistent viral infection or anemia (regressor cats) had decreased numbers of CFU-F (24% of the preinoculation CFU-F value) at 2 weeks after inoculation, but normal CFU-F numbers at 4, 6, 8, and 10 weeks after inoculation. In vitro incubation of bone marrow mononuclear cells from healthy cats with the 15,000-dalton envelope protein of FeLV resulted in decreased number of CFU-F (21% of that of untreated cultures). The number of CFU-F from bone marrow mononuclear cells incubated with the 27,000-dalton core protein of FeLV was similar to that from untreated cultures.
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PMID:Suppression of feline bone marrow fibroblast colony-forming units by feline leukemia virus. 283 64


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