Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cotton-wool spots and cytomegalovirus (CMV) retinitis are seen frequently in AIDS patients. Human immunodeficiency virus (HIV) infection of the retina has been proposed as a mechanism for the high incidence of retinal pathology. An autopsy study of the eyes from 25 consecutive cases of AIDS was performed using gross examination, light microscopy, trypsin digestion of retinal vasculatures, and immunohistochemistry to evaluate the possible role of HIV, as well as CMV, in the pathogenesis of retinitis and retinal vasculopathy. Brain tissue was studied in the first 20 of these cases to evaluate any correlation between retinal and central nervous system pathology. CMV retinitis was observed in 15 cases (60%). Cotton-wool spots were seen in nine cases (36%). CMV encephalitis was detected in four cases, whereas HIV encephalitis was noted in five cases. We were unable to demonstrate a correlation between CMV retinitis and CMV encephalitis. However, the number of cases studied was small, and the frequency of CMV encephalitis was low. On the other hand, bilateral CMV retinitis demonstrated a correlation to HIV encephalitis (P less than 0.005, Fisher's exact test). HIV infection of the retina was not detected by typical morphologic changes or immunohistochemistry. Immunohistochemistry localized CMV infection solely to areas of active retinitis. These findings suggest that bilateral CMV may serve as a marker of HIV encephalitis, possibly indicating a severely immunodepressed state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of HIV and CMV in the pathogenesis of retinitis and retinal vasculopathy in AIDS patients. 132 96

A novel membrane-bound serine esterase, named tryptase TL2, which is immunologically reactive with the antibody inhibiting induction of syncytia by human immunodeficiency virus-1 (HIV-1) (HATTORI, T., KOITO, A., TAKATSUKI, K., KIDO, H., and KATUNUMA, N., 1989, FEBS Lett., 248, 48-52), has been purified from a human T4+ lymphocyte clone. The enzyme has a molecular mass of 198 +/- 15 kDa, and is composed of two subunits of 32 kDa and four subunits of 28 kDa. The enzyme was strongly inhibited by the envelope glycoprotein gp120 of HIV-1, by synthetic peptides of V3 domains of gp120 s with the sequence GPGR in their center, which correspond to the principal neutralizing epitopes of the gp120s of various HIV-1 strains, by Kunitz-type inhibitors with the sequence GPCR in their active site, such as trypstatin, H130, and [Arg15, Glu52] aprotinin and by the microbial inhibitors leupeptin and antipain. This enzyme was specifically bound to the inhibitor V3 domain of gp120 of HIV-1, and this binding was blocked by the inhibitors of tryptase TL2, with a central motif GPCR or GPGR sequence in their center, but not by leupeptin and antipain without the motif. These findings suggest that tryptase TL2 is important in target site recognition and binding of HIV-1 in co-operation with CD4 receptor in the initial process of HIV-1 infection.
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PMID:A novel membrane-bound serine esterase in human T4(+)-lymphocytes is a binding protein of envelope glycoprotein gp120 of HIV-1. 168 71

Nevirapine (BI-RG-587) is a potent and specific non-nucleoside inhibitor of human immunodeficiency virus type-1 reverse transcriptase. The compound is non-competitive with respect to template, primer, and nucleoside triphosphates indicating that BI-RG-587 does not act directly at the catalytic site. The binding site for this inhibitor was investigated by employing an azido photoaffinity analogue, BI-RJ-70, to covalently label the enzyme. The resulting photoadduct was subjected to enzymatic digestion by trypsin and endoproteinase lys-C and a single, highly labeled peptide was identified as residues 174-199. Sequencing of this peptide identified Tyr-181 and Tyr-188 as labeled residues.
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PMID:Characterization of the binding site for nevirapine (BI-RG-587), a nonnucleoside inhibitor of human immunodeficiency virus type-1 reverse transcriptase. 171 87

The gp120 envelope glycoprotein of human immunodeficiency virus type 1 binds the cell surface protein CD4 with high affinity. Here we report the use of proteolysis to define regions of gp120 involved in CD4 binding. Cleavage of gp120 with Staphylococcus aureus V8 protease at residue 269 or with trypsin at residue 432 destroys CD4 binding. These same sites are protected from proteolytic cleavage by bound CD4. Cleavages at 64, 144, 166, 172, and 315 do not affect binding and are not protected by bound CD4, indicating that these regions are not critical for binding CD4. All proteolytic fragments found in coprecipitates with CD4 were covalently associated via disulfides and comprised complete gp120 molecules. Previous conclusions by Nygren et al. [Nygren, A., Bergman, T., Matthews, T., Jornvall, H. & Wigzell, H. (1988) Proc. Natl. Acad. Sci. USA 85, 6543-6546] that both large and small (95-kDa and 25-kDa) V8 proteolytic fragments bind CD4, independently, are not distinguished by their experiments from the result found here that the small fragment immunoprecipitates with CD4 while disulfide-linked to the larger fragment.
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PMID:CD4-binding regions of human immunodeficiency virus envelope glycoprotein gp120 defined by proteolytic digestion. 176 44

Deletions were constructed within a functional human immunodeficiency virus type 1 (HIV-1) proviral clone in order to assess the role of the envelope protein in virus particle formation. A graded exonuclease deletion technique was used to produce 12 clones with deletions of 175-308 nucleotides in the first conserved domain of envelope. This included 9 clones with frameshift deletions and 3 clones with in-frame deletions. Isogenic pairs of env deletion clones were produced with or without an additional deletion in the vif and vpr genes. Upon transfection, all clones produced virus particles, as determined by p24 antigen, reverse transcriptase, and sucrose gradient assays with conditioned media. Virus particles produced from clones with deletions in env or vif and vpr, or both regions, banded on sucrose gradients with a mobility similar to that of virus produced by the parental clone. The p24 gag capsid protein in the particles was resistant to trypsin, but the particles were disrupted by treatment with Triton X-100, suggesting the presence of a surrounding lipid bilayer. Furthermore, electron microscopic studies revealed both mature and immature virus particles derived from COS cells transfected with the env deletion clones. Cocultivation experiments with lymphoid cells and cells transfected with each of the env deletion clones demonstrated that the virus particles were noninfectious.
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PMID:Formation of noninfectious HIV-1 virus particles lacking a full-length envelope protein. 182 17

The complete amino acid sequence of a new abortifacient protein, karasurin, was determined. Karasurin, which was isolated from fresh root tubers of Trichosanthes kirilowii Maximowicz var, japonicum Kitamura (Cucurbitaceae), was a highly basic protein with pI 10.1 and molecular weight of 28,000. Intact karasurin was cleaved with cyanogen bromide, lysyl endopeptidase, formic acid and 2-(2'-nitrophenyl-sulfenyl)-3-methyl-3-bromoindolenine (BNPS-skatole), respectively. Cleavages with N-bromosuccinimide (NBS), trypsin and pepsin were performed for the fragments. The resultant peptide fragments were separated by gel filtration chromatography, reversed-phase high performance liquid chromatography (HPLC) or gel filtration HPLC following sequence analyses by automated Edman methods. Karasurin consists of 246 or 247 amino acid residues with a calculated molecular weight of 27,144 or 27,215 differing only at the C-terminus with the addition of alanyl residue. Two C-terminal sequences were identified as Asn-Asn-Met-OH and Asn-Asn-Met-Ala-OH by sequence analyses and hydrazinolysis, but there was no micro-heterogeneity in other peptides analysed. The sequence of karasurin revealed a considerable similarity to that of trichosanthin and alpha-trichosanthin, which are known as abortifacient, ribosome-inactivating and anti human immunodeficiency virus (HIV) (the virus causing acquired immunodeficiency syndrome (AIDS) proteins, with 93% and 98% identity, respectively.
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PMID:The complete amino acid sequence of an abortifacient protein, karasurin. 191

The CD4 molecule has several biological functions, physiologically as a receptor for major histocompatibility complex class II molecules on antigen-presenting cells, and pathologically as a receptor for human immunodeficiency virus (HIV) by its binding to the HIV envelope glycoprotein gp 120. The frequency of CD4+ cells has been shown to correlate positively with both susceptibility and cytopathogenic effect by HIV. To determine if CD4 expression varied during the cell cycle, a CD4-expressing monocytoid cell line, U 937 clone 16, was synchronized with regard to cell growth. The CD4 antigen was analysed with regard to expression, density and rate of reappearance after treatment with trypsin, during the different phases of the cell cycle. The CD4 reappearance rate was found to be maximal during the S phase. This was followed by an increased expression and density in the late S/G2 phase. Thus a cell cycle-dependent expression of CD4 molecules on the cell surface was observed.
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PMID:Cell cycle-dependent expression of CD4 antigen in a monocytoid cell line. 192 11

A novel membrane-bound serine esterase, named tryptase TL2, which is immunologically reactive with the antibody inhibiting induction of syncytia by human immunodeficiency virus-1 (HIV-1) (Hattori, T., Koito, A., Takatsuki, K., Kido, H., and Kutunuma, N. (1989) FEBS Lett., 248, 48-52), has been purified from a human T4+ lymphocyte clone. The enzyme has a molecular mass of 198 +/- 15 kDa, as judged by gel-permeation liquid chromatography, and is composed of two subunits of 32 kDa and four subunits of 28 kDa, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Studies with model peptide substrates showed that the enzyme preferentially recognized L-arginine and cleaved Boc-Gln-Gly-Arg-4-methyl-coumaryl-7-amide and Boc-Gln-Ala-Arg-4-methyl-coumaryl-7-amide with high efficiency at a pH optimum of 8.5. The enzyme was strongly inhibited by the envelope glycoprotein gp 120 of HIV-1, by synthetic peptides with the sequence GPGR in their center, which corresponds to the principal neutralizing epitope of the gp 120s of various HIV-1 strains, by Kunitz-type inhibitors with the sequence GPCR in their active site, such as trypstatin, HI30, and [Arg15, Glu52]aprotinin and by the microbial inhibitors leupeptin and antipain. Studies on the subcellular distribution of tryptase TL2, immunohistochemical analysis, and cell surface radioiodination indicated that the enzyme is mainly localized in the plasma membrane.
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PMID:A novel membrane-bound serine esterase in human T4+ lymphocytes immunologically reactive with antibody inhibiting syncytia induced by HIV-1. Purification and characterization. 197 28

Located close to the crown of the V3 type-specific neutralization loop of the human immunodeficiency virus type 1 (HIV-1) (IIIB) SU glycoprotein gp120, are several potential sites that should be susceptible to proteolytic cleavage by enzymes of trypsinlike or chymotrypsinlike specificity, or by aspartic proteinases. The linkages potentially sensitive to chymotryptic/aspartic proteinase cleavage are retained also within the equivalent domain of HIV-2 (ROD) gp105. We show that thrombin and tryptase cleave HIV-1 gp120 specifically at the tryptic site (GPGR decreases AFVT), and that cathepsin E, an endosomal aspartic proteinase, cleaves at the chymotrypsinlike site (GPGRAF decreases VT). HIV-2 gp105 is also cut by cathepsin E at a site (QIML decreases MSGH) in its V3 loop. Cleavage of HIV-1 gp120 by thrombin is enhanced by sCD4 binding, but is prevented by transient exposure of gp120 to nonionic detergent. Thrombin treatment of HIV-1 gp120 destroys the binding sites for some neutralizing monoclonal antibodies (MAbs) on the V3 loop, but does not affect the affinity of gp120 for sCD4. Conversely, binding of neutralizing MAbs to the HIV-1 V3 loop prior to addition of thrombin or cathepsin E blocks the cleavage reactions, and the binding of some HIV-positive sera to gp120 blocks thrombin cleavage. Analysis of published sequences suggests that all HIV-1, HIV-2, and simian immunovirus (SIV) isolates contain potential proteolytic cleavage sites at similar positions in their V3 loops or equivalent domains. We suggest that cleavage of the V3 loop by a cell surface or endosomal proteinase occurs during the HIV-cell fusion reaction, and that neutralizing antibodies directed against the V3 loop might act by inhibition of this reaction.
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PMID:The V3 loops of the HIV-1 and HIV-2 surface glycoproteins contain proteolytic cleavage sites: a possible function in viral fusion? 201 14

The human immunodeficiency virus-1 (HIV-1) Tat protein has previously been shown to transactivate the HIV-1-LTR when added exogenously to HeLa, H9 lymphocytic and U937 promonocytic cells growing in culture. Here we show that Tat enters these cells by adsorptive endocytosis. Tat appears to bind non-specifically to the cell surface, with greater than 10(7) sites per cell. A specific receptor was not detected by protein crosslinking experiments, and uptake was not affected by treating cells with trypsin, heparinase or neuraminidase. Uptake and transactivation could be inhibited by incubation with heparin, dextran sulfate, an anti-Tat monoclonal antibody, or by incubation at 4 degrees C. In contrast, transactivation by Tat was markedly stimulated by the addition of basic peptides, such as Tat 38-58 or protamine. Fluorescence experiments with rhodamine-conjugated Tat show punctate staining on the cell surface and then localization to the cytoplasm and nucleus. The lack of a specific receptor makes it unclear whether Tat uptake is biologically important in HIV infection, however, the efficiency of uptake raises the possibility that Tat may be useful for delivery of protein molecules into cells.
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PMID:Endocytosis and targeting of exogenous HIV-1 Tat protein. 205 Jan 10


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