Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Recombinant retroviral vectors can efficiently transduce and express foreign genes in mammalian cells. We have examined the utility of retroviral vector-mediated gene transfer to deliver genes which encode human immunodeficiency virus type I (HIV) antigens capable of stimulating specific immune responses. Murine fibroblast cell lines were transduced with a nonreplicating murine retroviral vector carrying the gene encoding the HIV-IIIB envelope protein and were shown to express the gp160/120 protein. Mice immunized with syngeneic vector-transduced cells developed CD8+, class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) specific for targets expressing the HIV envelope protein. The CTL also exhibited lytic activity on target cells coated with synthetic peptides derived from the gp120 V3 hypervariable region of both the HIV-IIIB and HIV(MN) isolates. Following adoptive transfer in a murine tumor model, these CTL were shown to be effective in vivo by their ability to eliminate established tumor cells expressing the HIV protein. Vector-transduced syngeneic cells were also capable of eliciting HIV envelope-specific antibody responses in immunized mice. Sera obtained from these mice were found to bind to the HIV-IIIB gp160 protein as well as a peptide-defined neutralizing antibody epitope contained within the V3 domain of gp120. These sera exhibited virus-neutralizing activity in that they markedly reduced the ability of HIV to infect and form syncytia of a human T-cell line. This is the first demonstration that cells transduced with a retroviral vector encoding the HIV-IIIB envelope protein are capable of inducing effective HIV-specific cellular and humoral immune responses in mice.
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PMID:Induction of HIV-specific CTL and antibody responses in mice using retroviral vector-transduced cells. 193 Dec 34

Our results demonstrate that the formation of intracellular complexes between the envelope glycoprotein precursor gp160 of human immunodeficiency virus type 1 and CD4 is a major event, leading to the disappearance of CD4 at the cell surface of infected U937 cells. Using both productively and defectively infected clones of U937 cells, we assessed the effect of CD4-gp160 intracellular association on the maturation of both proteins. Pulse-chase labeling followed by sequential immunoprecipitation was used to analyze the processing of both free and associated CD4 and gp160, and the results showed that the trimming, proteolytic cleavage, and degradation of gp160 were completely abrogated after intracellular binding to CD4. Similarly, the maturation process which normally transforms 80% of CD4 to a partially endoglycosidase H-resistant species was also impaired subsequent to the formation of these complexes. A comparison of gp160 maturation either in free form or as a CD4 complex revealed that neither inefficient transport nor degradation of gp160 can account for the observed blockage of CD4 maturation. Moreover, this impairment was independent of gp120 and gp41, since a defective clone of human immunodeficiency virus type 1-infected cells, unable to cleave gp160, showed binding of CD4 and inhibition of CD4 transport and maturation with the same efficiency as occurred in productively infected cells. Expression of gp160 is thus necessary and sufficient to cause CD4 receptor down-modulation for both productively and defectively infected cells.
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PMID:Inhibition of gp160 and CD4 maturation in U937 cells after both defective and productive infections by human immunodeficiency virus type 1. 194 41

Untreated urine specimens from 358 patients (344 attending genito-urinary medicine clinics, 14 haemophiliacs) and 353 blood donors were tested blind by a simple IgG-capture particle-adherence test (GACPAT) and a rapid IgG-capture enzyme-linked immunosorbent assay (GACELISA) for antibody to human immunodeficiency virus (anti-HIV). All 158 urine specimens from seropositive subjects were anti-HIV positive by GACPAT and 157 of them (99.4%) were positive by GACELISA. Tests on 553 urine specimens from seronegative subjects gave two repeatable false-positive reactions by GACPAT (0.4%) and none by GACELISA. By means of a modified procedure anti-gp160 was detected by commercial western blot in the urine of 44 of 45 seropositive subjects examined. IgG-capture assays will detect anti-HIV in unconcentrated urine and so allow a diagnosis in circumstances when blood sampling is impracticable.
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PMID:Preliminary report: accurate assays for anti-HIV in urine. 197 62

A procedure to diagnose the infections by the human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) was proposed. The specimens were first screened by a mixed enzyme immunoassay (EIA) for the presence of antibodies to HIV-1 as well as to HIV-2. Those screened positive were thereafter confirmed and differentiated their antibody reactivities toward the antigens of HIV-1 and HIV-2 by Western blot (WB). This procedure was found to be one hundred percent accurate to diagnose 66 coded specimens with well defined seroreactivities to HIV-1 from Centers for Disease Control (CDC). While its accuracy in HIV-2 antibody testing could not be evaluated in the present study owing to the lack of HIV-2 standard reference specimens. With this procedure, six out of each of two groups of 176 foreigners and 719 individuals who visited the Taipei Municipal Venereal Disease Control Institute (TMVDCI) were screened repeatedly reactive by the mixed EIA. By WB only four of the first six and two of the second six were confirmed HIV-1 positive. Their antibody reactivities toward HIV-2 antigens were either absent or significantly much lower than those toward HIV-1 antigens. Furthermore, none reacted to the env proteins gp160 and gp120 of HIV-2. We therefore concluded that out of the 895 test individuals, only six were confirmed infected with HIV-1. There were neither HIV-2 infections nor dual infections. The similar pathogenicity and trans mission of HIV-2 as of HIV-1 justify an equal appreciation for HIV-2 testing. The present study indicated that a procedure starting with a mixed EIA aimed to diagnose HIV-1 as well as HIV-2 did not have any adverse effects on HIV-1 testing.
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PMID:Application of a procedure starting with an HIV-I/HIV-2 mixed EIA. 198 37

The gp41 transmembrane protein of human immunodeficiency virus type 1 (HIV-1) contains a hydrophobic membrane-spanning domain that serves to anchor the gp120-gp41 complex on the surface of infected cells and virions. To study the requirements for membrane anchorage, conservative amino acid substitutions in three residues at a time were made within this hydrophobic gp41 region. The complete gp160 precursor as well as the gp120 exterior envelope glycoprotein were exported into the supernatant of expressing cells for two mutants with amino acid substitutions in residues 687-689 and 697-699. The soluble gp160 molecules exhibited a binding ability for CD4 on the surface of SupT1 cells that was 33-36% that of the soluble gp120 glycoproteins. These results implicate residues 687-689 and 697-699 as important components of the stop-transfer signal that anchors the gp160 envelope glycoprotein precursor in the membrane. The data also suggest that characteristics in addition to hydrophobicity are required for stop-transfer signals.
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PMID:Identification of membrane anchorage domains of the HIV-1 gp160 envelope glycoprotein precursor. 198 54

The V3 loop, located near the middle of the surface envelope glycoprotein gp120, is the major neutralizing domain of human immunodeficiency virus type 1 (HIV-1). Although the majority of the V3 loop is highly variable between different strains of HIV-1, a Gly-Pro-Gly-Arg motif at the tip of the loop is highly conserved. To determine whether this region plays a role in fusion mediated by the HIV-1 envelope glycoproteins, we introduced seven single-amino-acid changes in the V3 loop. The mutant envelope glycoproteins were expressed from an HIV-1 envelope expression vector and analyzed for their ability to induce cell fusion in the absence of virus replication. Our results indicated that single-amino-acid changes in the V3 loop were capable of completely abolishing or greatly reducing the ability of the HIV-1 envelope glycoproteins to induce cell fusion, thereby identifying the V3 loop as a fusion domain of HIV-1. Mutations in the highly conserved tip of the loop or in a nonconserved region flanking the highly conserved tip had no effect on envelope glycoprotein synthesis, processing, transport, or binding to the CD4 receptor molecule. Mutation of the putative disulfide bridge-forming Cys at residue 336 blocked gp160 cleavage and CD4 binding.
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PMID:Identification of the principal neutralizing determinant of human immunodeficiency virus type 1 as a fusion domain. 198 97

The effects of C-terminal and internal deletions on the synthesis, transport, biological properties, and antigenicity of the human immunodeficiency virus type 1 envelope protein were determined. A family of recombinant vaccinia viruses that express N-terminal overlapping env proteins of 204, 287, 393, 502 (full-length gp120), 635, 747, and 851 (full-length gp160) amino acids was constructed. All of the proteins were detected in intra- and extracellular forms which differed in the extent of glycosylation. The 747- and 851-amino-acid proteins were cleaved, were expressed on the surface of infected cells, and bound CD4. The 635-amino-acid env protein was cleaved inefficiently, and both the precursor and product were secreted, indicating absence of the transmembrane sequence. The 635- as well as the 502-amino-acid protein, which was also largely secreted, could still bind CD4. Unexpectedly, the 393-amino-acid protein was anchored in the plasma membrane, but neither it nor smaller proteins bound to soluble CD4. When amino acids at the gp120-gp41 junction were deleted, proteolytic cleavage of gp160 did not occur. Nevertheless, gp160 was inserted into the plasma membrane and bound soluble CD4. The predominant conserved B-cell epitopes were mapped to gp41 and the C terminus of gp120, whereas cytotoxic T-cell epitopes were distributed throughout the length of the glycoproteins.
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PMID:Biological and immunological properties of human immunodeficiency virus type 1 envelope glycoprotein: analysis of proteins with truncations and deletions expressed by recombinant vaccinia viruses. 198 2

The highly glycosylated envelope glycoprotein (gp 160) of human immunodeficiency virus (HIV) interacts with the CD4 molecule present on the membrane of CD4+ cells and is involved in the pathobiology of HIV infection. Lectins bind glycoproteins through non-covalent interactions with specific hexose residues. The mammalian C-type lectin bovine conglutinin was examined for its ability to interact with recombinant gp160 (rgp160) produced in vaccinia virus-infected BHK21 cells. Specific binding of conglutinin to rgp160 was demonstrated by ELISA. The interaction of bovine conglutinin with rgp160 was calcium-dependent, which is characteristic of the binding of a C-type lectin to its ligand, and the binding was inhibited in a dose-dependent manner with N-acetyl-D-glucosamine. Deglycosylation of rgp160 abrogated the conglutinin binding. In addition, conglutinin exerted a dose-dependent inhibition of the binding of rgp160 to the CD4 receptor on CEM 13 cells, as demonstrated by FACS analyses. These results indicate that conglutinin may inhibit the infection with HIV-1 through its interaction with the viral envelope glycoprotein.
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PMID:Conglutinin binds the HIV-1 envelope glycoprotein gp 160 and inhibits its interaction with cell membrane CD4. 199 9

Incubation of normal human nonadherent and T-cell-depleted bone marrow cells with HIVIIIB at multiplicities of infection (MOI) ranging from 0.0001:1 to 1:1 reverse transcriptase (RT) units resulted in the dose-dependent suppression of the in vitro growth of erythroid burst-forming unit (BFU-E), granulocyte-macrophage (CFU-GM), and T-lymphocyte (CFU-TL) colonies of progenitor cells. Maximum inhibition of colony formation was observed at a 1:1 ratio of virus to bone marrow cells. At this MOI, BFU-E and CFU-GM colonies were inhibited by 60 to 80%, while CFU-TL colonies were totally suppressed. Inhibition of colony formation was also observed at an MOI of 0.1:1 but not with further log dilutions of the virus. Incubation of the virus with antibody to gp160 resulted in the complete reversal of stem cell suppression and the normalization of colony growth in vitro. For BFU-E and CFU-GM colonies, this reversal was observed with dilutions of antibody up to 1:100 and was no longer observed at titers greater than 1:500. The CFU-TL colony number normalized at titers between 1:10 and 1:50. Human immunodeficiency virus (HIV) also suppressed by 50% the growth of colonies derived from CD34+ stem cell fractions. Infection of CD34+ cells and T-cell-depleted, nonadherent cell fractions was demonstrated by detection with HIV-specific DNA probe following amplification by polymerase chain reaction. The results suggest that HIV can directly infect human bone marrow progenitor cells and affect their ability to proliferate and give rise to colonies in vitro. The results indicate a direct role for the virus in bone marrow suppression and a possible mechanism for the cytopenias observed in patients with AIDS.
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PMID:In vitro suppression of normal human bone marrow progenitor cells by human immunodeficiency virus. 200 42

To gain insights into the structure-function relationship of the envelope (env) glycoprotein of the human immunodeficiency virus type 1 (HIV-1) we have generated a vaccinia virus (VV) recombinant (VV-14kENV) that expresses a fusion protein (14k-env) consisting of the VV 14-kDa envelope protein (110 amino acids) fused at the C-terminus with HIV-1 env protein (816 amino acids). The 14k-env protein displayed unique structural properties in virus-infected cells. This protein was recognized by 14 kDa-specific antisera as well as HIV-1 env antisera. It was not cleaved during virus infection of cultured cells of various origins, it was stable, it was not released to the medium, and it was not incorporated into virions. Instead of a predicted 174-kDa protein, two proteins of about 110 and 100 kDa were observed. The size reduction of the fusion protein was due to limited glycosylation (110 kDa) and formation of unglycosylated protein (100 kDa). The 14k-env protein formed oligomeric structures and was exposed on the cell surface after virus infection. When mice were inoculated with the recombinant virus that expresses the 14K-env fusion protein, humoral immune response against gp160 was observed. Our findings suggest that 14k-env protein might display novel immunogenic properties.
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PMID:Structural properties of HIV-1 Env fused with the 14-kDa vaccinia virus envelope protein. 201 47


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