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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyanionic compounds were used to inhibit infectivity of human immunodeficiency virus in vitro. Suramin, Evans blue, and Trypan blue were shown to inhibit syncytia formation normally observed when HIV-1-infected cells are cocultured with CD4+ cells. The inhibition was more pronounced with Evans blue than with any of the other polyanions studied. The inhibitory effect was significantly weaker in HIV-2 systems. However, the reverse transcriptase activities of both types of viruses were inhibited by Evans blue. Another polyanionic compound, phosphorothioate 28-mer cytidine homopolymer (SdC28) was shown to inhibit syncytium formation induced by HIV-1-and HIV-2-infected cells in an identical manner. Evans blue showed partial blocking of gp120 binding to CD4 in a solid-phase enzyme-linked immunosorbent assay (ELISA). These results suggest that the polyanionic dyes may exert their antiviral effects, at least in part, by interfering with the binding and fusion of HIV with susceptible T cells.
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PMID:Effect of Evans blue and trypan blue on syncytia formation and infectivity of human immunodeficiency virus type I and type II in vitro. 171 43

Infection with the human immunodeficiency virus (HIV-1) often produces a set of neuropsychiatric dysfunctions which have been termed the AIDS dementia complex. This complex appears due to the infection of brain cells by HIV-1. If so, brain cells might be expected to contain a binding site for the same viral envelope glycoprotein that enables HIV-1 to bind to other cells (e.g. CD4+ T-cells), gp120. The present study shows that the cells of the brain-derived U-138MG, U-373MG, SK-N-MC and SK-N-SH cell lines bind gp120 in an inhibitable fashion. Binding of gp120 to these cells is inhibited by the dyes Aurintricarboxylic acid (ATA) and Evans blue (EB), which are known to inhibit specific gp120 and HIV-1 binding, and block HIV-1 infection, in CD4-expressing cells. Binding is not inhibited by Aurin, a dye related to ATA but lacking its anti-HIV effects. As expected, anti-CD4 antibodies are ineffective in blocking gp120 binding to brain-derived cells. These results suggest that human brain-derived cells possess a specific binding site for gp120 that is not the CD4 antigen.
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PMID:Brain-derived cells contain a specific binding site for Gp120 which is not the CD4 antigen. 193 87

We studied the ability of several polyionic compounds, previously shown to have activity in vitro against human immunodeficiency virus (anti-HIV) to block binding of anti-CD4 and recombinant HIV gp120 to the CD4 receptor on human lymphocytes. We found that Evans blue and aurin tricarboxylic acid could completely inhibit binding of anti-CD4 (Leu3a) and rgp120 and have selectivity for the CD4 receptor. A number of other compounds, including dextran sulfate and heparin had no effect on binding of rgp120 and were shown to be nonspecific for inhibition of binding of monoclonal antibodies to different T-cell receptors. Studies using a number of membrane-active drugs showed that changes in membrane potential or ion fluxes were not involved in the inhibition of binding of rgp120 by Evans blue or aurin tricarboxylic acid.
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PMID:Polyionic compounds selectively alter availability of CD4 receptors for HIV coat protein rgp120. 197 10

The first step in the replicative cycle of human immunodeficiency virus type 1 (HIV-1) is binding of the virions to the cellular CD4 receptor. This process may be considered as an important target for chemotherapeutic agents against acquired immune deficiency syndrome (AIDS). A method has now been devised whereby virion binding to the cell membrane was visualized by an indirect immunofluorescence assay using human anti-HIV-1 serum, rabbit anti-human-IG-F(ab')2-fluorescein isothiocyanate, and flow cytometry. Heparin, dextran sulfate, and pentosan polysulfate suppressed HIV-1 binding to MT-4 cells at concentrations that protected the cells against HIV-1 cytopathogenicity. Dextran and dermatan sulfate, two compounds that are inactive against HIV-1, had no inhibitory effect on the binding of HIV-1 to the cells. The potent and selective HIV-1 inhibitor azidothymidine (AZT) did not affect virus binding to the cells, whereas suramin partially blocked HIV-1 binding to the cells at concentrations that fully protected MT-4 cells against destruction of HIV-1. Our immunofluorescence assay thus demonstrated that suramin not only acts as an inhibitor of reverse transcriptase but also interferes with virus-cell binding. Also, Evans blue, an anionic dye structurally related to suramin, partially inhibited HIV-1 attachment to the cells. The present method permits a quantitative determination of the inhibitory effect of anti-HIV-1 agents on virion-cell binding.
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PMID:Flow cytometric method to demonstrate whether anti-HIV-1 agents inhibit virion binding to T4+ cells. 246 2

We investigated LEC rats immunopathologically which spontaneously developed hepatitis to find out the genesis, in comparison with non-hepatitis LEA (Long Evans Agouti) rats. 1) Wet weights of the spleen and thymus of 6-week old LEC rats were significantly lighter than those of LEA rats of the same age. 2) Serum IgG (Immunoglobulin G) in LEC rats remained markedly low after the age of two months and IgG antibody formation to SRBC (Sheep Red Blood Cell) as detected by plaque assay was also significantly suppressed. On the other hand, IgM antibody formation to SRBC was significantly suppressed through serum IgM level in LEC rats was normal or rather increased. 3) Blastogenic responses of spleen cells to PHA and Con A were much more suppressed in LEC rats than in LEA rats. 4) Cytostatic activity of intraperitoneal macrophages against tumor cells was more evident in LEC rats than in LEA rats, but there was no difference in NK (natural killer) activity between the two rat strains. From these results, it is speculated that spontaneously hepatitis-developing LEC rats possess T and B cell deficiency (combined immunodeficiency) and that the increase of macrophage and NK cell activities are linked to the genesis of developing hepatitis.
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PMID:[Combined immunodeficiency in LEC (Long Evans Cinnamon) rats with spontaneous hepatitis]. 279 59

We report here a human-immunodeficiency-virus-type-1 (HIV-1) recombinant reverse transcriptase (RT) engineered to contain a 26-amino-acid linker insertion from the tether domain of feline leukaemia virus (FLV) RT. The chimaeric protein was expressed in Escherichia coli and migrated on SDS/PAGE as a 68 kDa band. A monomeric form of the chimaeric HIV-1 RT has been prepared by the coordinated applications of immobilized-metal-affinity chromatography and gel filtration on Superose 12 columns. The monomeric nature of this chimaeric HIV-I RT was further characterized by cross-linking studies using disuccinimidyl suberate. The RNA-dependent DNA polymerase activity of the monomeric chimaeric HIV-1 RT was 35% that of the heterodimeric (p66/p51) HIV-1 RT. These results support our recent studies on the monomeric polymerase domain (p51 RT) which exhibited an RNA-dependent DNA polymerase activity equal to 33% of that of the p66/p51 heterodimeric HIV-1 RT (Evans, Kezdy, Tarpley and Sharma [1993] Biotechnol. Appl. Biochem. 17, 91-102). The inability of the monomeric chimaeric HIV-1 RT to display polymerase activity like that of the heterodimeric HIV-1 RT is attributed to a decrease in the processive rate of DNA synthesis (75%) and DNA binding (65%). However, the monomeric chimaeric HIV-1 RT (p68) exhibited RNAase H activity like that of the heterodimeric form (p66/p51) of HIV-1 RT. These results suggest that the linker insertion from FLV RT does not interfere with the RNAase H activity associated with the monomeric HIV-1 RT.
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PMID:Engineering of the human-immunodeficiency-virus-type-1 (HIV-1) reverse transcriptase gene to prevent dimerization of the expressed chimaeric protein: purification and characterization of a monomeric HIV-1 reverse transcriptase. 751 79

Long-Evans Cinnamon (LEC) rats bear a congenital deficiency in CD4+8- thymocytes and consequently a deficiency in helper T cell function. This mutation is caused by a single recessive gene referred to as thid (T helper immunodeficiency). It has been reported that rat immunoglobulin(Ig) G2a subclass is a counterpart of the mouse IgG1. Serum IgG2a levels in LEC rats were ten-fold lower than those of normal rats. To identify a cause of low IgG2a levels in LEC rats, we made backcross rats, (F344 x LEC)F1 x LEC, and examined linkage to the thid mutation. The serum IgG2a levels of rats showing thid/thid phenotype were much lower than those of rats showing +/thid phenotype. This indicates that the thid mutation correlates with low level of IgG2a subclass. Furthermore, LEC rat B cells were shown to secret IgG2a normally when these were stimulated with LPS and IL-4, suggesting that a cause of low level of IgG2a was due to defect of T cell function but not due to B cell disfunction in LEC rats. These results confirm the idea that T-helper (Th) function is necessary for the class switch to IgG2a subclass in rats.
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PMID:Low level of immunoglobulin G2a subclass correlates with a deficiency in T helper cell function in LEC mutant rats. 754 12

The polymerase domain of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, called the p51 reverse transcriptase (p51 RT), was expressed in Escherichia coli. The recombinant protein also contained an N-terminal affinity tag designed to facilitate its purification by immobilized metal affinity chromatography. The purified p51 RT is a predominantly monomeric protein and it catalyses RNA-dependent DNA polymerization with poly(rA).oligo(dT) as the template.primer. Recently we have also reported the isolation of the recombinant RNAase H domain of HIV-1 RT that is enzymically active (Evans, Brawn, Deibel, Tarpley and Sharma [1991] J. Biol. Chem. 266, 20583-20585). The latter directly inhibits the RNA-dependent DNA polymerase activity of p51 RT. Kinetic experiments show that the p15 RNAase H-mediated inhibition of p51 RT is competitive with respect to the poly(rA).oligo(dT) template.primer (Ki = 320 +/- 50 nM), and it does not interfere directly with the binding of dTTP to the enzyme. Thus the kinetic behaviour is consistent with the binding of p15 RNAase H at or near the template.primer-binding site in this replicase. If the binding of the p15 RNAase H involves only a small segment of this protein, then identification of that segment may open up new opportunities towards the design of novel inhibitors of RNA-dependent DNA polymerase activity.
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PMID:Inhibition of the RNA-directed DNA polymerase activity of a recombinant HIV-1 p51 reverse transcriptase by a p15 ribonuclease H domain. 767 7

Long-Evans Cinnamon (LEC) mutant rats were reported to exhibit a deficiency in the serum immunoglobulin (Ig) G1. The phenotype determining the basal level of IgG1 was tentatively designated as immunoglobulin subclass regulator-1 (Igsr-1), and normal rats and LEC rats were categorized into Igsr-1A (normal expression of IgG1) and Igsr-1B (low expression of IgG1), respectively. In this report we examined genetic trait of this phenotype in LEC rats. The serum IgG1 levels in F1 hybrids produced by mating LEC rats (Igsr-1B) with normal rats (Igsr-1A) were intermediate level, indicating that Igsr-1 behaves as a co-dominant genetic trait. When backcross rats were examined, serum IgG1 levels varied between those in normal and LEC rats without clear segregation, indicating that Igsr-1 is controlled by multiple genes. Furthermore, the serum IgG1 level in each backcross rat did not correlate to another recessive mutant genotype, thid (T-helper immunodeficiency). These data suggest that the deficiency in serum IgG in LEC rats is independent of the deficiency in helper T cell function, but might be due to the multiple deficiency in as-yet-unidentified mechanisms.
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PMID:Inheritance of immunoglobulin subclass regulator-1 (Igsr-1) in LEC mutant rats. 786 88

Several domains of CD4 have been suggested to play a critical role in events that follow its binding to the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120-gp41). It has been reported previously that cells expressing a chimeric molecule consisting of the first 177 residues of human CD4 attached to residues from the hinge, transmembrane, and cytoplasmic domains of human CD8 did not form syncytia with HIV-1-infected cells (L. Poulin, L.A. Evans, S. Tang, A. Barboza, H. Legg, D.R. Littman, and J.A. Levy, J. Virol. 65: 4893-4901, 1991). In contrast, we found that the hybrid CD4.CD8 molecule expressed in human cells did render them susceptible to fusion with cells expressing HIV-1IIIB or HIV-1RF envelope glycoproteins encoded by vaccinia virus recombinants, but only after long lag times. The lag time of membrane fusion mediated by the hybrid CD4.CD8 molecule was fivefold longer than that for the wild-type CD4 molecule. However, the rate of binding to and the affinity of soluble gp120 for membrane-associated CD4.CD8 were the same as for CD4. Both molecules were laterally mobile, as determined by patching experiments. Coexpression of the CD4.CD8 chimera with wild-type CD4 did not lead to interference in fusion but had an additive effect. Therefore, the proximal membrane domains of CD4 play an important role in determining the kinetics of postbinding events leading to membrane fusion. We hypothesize that the long lag time is due to the inability of the CD4.CD8-gp120-gp41 complex to undergo the rapid conformational changes which occur during the fusion mediated by wild-type CD4.
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PMID:Cell fusion mediated by interaction of a hybrid CD4.CD8 molecule with the human immunodeficiency virus type 1 envelope glycoprotein does occur after a long lag time. 841 50


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