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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of CD4, the principle receptor for HIV-1, is not sufficient for viral entry into most non-human and rare human cell lines. Construction of HIV-1 susceptible heterokaryons and a hybrid cone by fusion of HeLa cells and the HIV-1 resistant human cell line U373-CD4 were previously reported by us. These results suggested that U373-CD4 lack a cofactor(s) which is essential for HIV-1 entry and can be supplied by HeLa cells. Now the construction of multiple stable U373-CD4/HeLa whole cell and microcell hybrid clones are described, two of which are highly susceptible to HIV-1. Using these hybrids it is demonstrated that expression of CD4 and CD26, the T cell activation antigen dipeptidyl peptidase IV recently proposed as a CD4 cofactor necessary for HIV-1 infection, are not sufficient for HIV-1 entry. This panel of HIV-1 resistant and susceptible hybrids provides a rapid, simple assay for testing the role of other candidate cofactor molecules (e.g., fusin) that may be required for HIV-1 entry into human cells. Further, the method described by us for constructing HeLa microcells should permit the construction of murine-HeLa microcell hybrids, thus providing ideal reagents for determining which human chromosome(s) are needed to confer HIV-1 susceptibility onto non-human cells.
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PMID:Human immunodeficiency virus type-1 susceptible whole cell and microcell hybrids. 890 22

Recent data in the literature suggest that the HIV-1 Tat(1-86) protein exhibits immunosuppressive effects. Moreover, Tat was found to interact with dipeptidyl peptidase IV (DP IV), which is identical to the T cell activation marker CD26. Here we show that the N-terminal amino acid sequence of Tat is essential for the inhibition of DP IV-catalyzed IL-2(1-12) degradation. N-terminal modification of Tat with rhodamine prevented inhibition of enzymatic activity of DP IV as well as suppression of DNA synthesis of mitogen-stimulated human T cells. Moreover, natural peptides containing the X-X-Pro N-terminal motif of Tat also inhibited DP IV activity. These data suggest the existence of endogenous immunomodulatory oligopeptides which influence immune cell proliferation and differentiation via DP IV as does HIV-1 Tat.
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PMID:The N-terminal X-X-Pro sequence of the HIV-1 Tat protein is important for the inhibition of dipeptidyl peptidase IV (DP IV/CD26) and the suppression of mitogen-induced proliferation of human T cells. 892 85

Phenylalanyl-pyrrolidine-2 nitrile (Phe-pyrr-2-CN) and arginyl(PMC)-pyrrolidine-2-nitrile (Arg(PMC)-pyrr-2-CN) are two dipeptidyl peptidase IV/CD26 (DPP-IV/CD26) inhibitors designed and synthesized by our group. These two compounds suppress the enzymatic activity of DPP-IV/CD26 in a competitive and reversible manner. Pretreatment of CEM cells with either of the compounds yielded a marked albeit transient reduction of HIV infection, as measured by HIV1 p24 production, RT activity and syncytium formation. The ID50 value of the Phe-Pyrr-2-CN and Arg(PMC)-pyrr-2-CN in HIV1 inhibition was 5.3 microM and 2.4 microM, respectively. Administration of either of the DPP-IV/CD26 inhibitors 1 h after HIV1 infection did not suppress HIV1 production. An analog whose inhibitory activity toward DPP-IV/CD26 was abolished by blocking the N-terminal of Phe-pyrr-2-CN with the 9-fluorenymethyloxycarbonyl (Fmoc) group had no effect on HIV1 infection. An additive effect of HIV1 inhibition was observed in combinations of either of the DPP-IV/CD26 inhibitors with CD4 monoclonal antibody. These results suggest that DPP-IV/CD26 enzymatic activity may play a role in facilitating HIV1 infection of human CD4+T cells at the entry process. DPP-IV/CD26 inhibitors may therefore have potential use in combination with other drugs to prevent HIV1 transmission.
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PMID:Inhibition of human immunodeficiency virus type 1 infection in a T-cell line (CEM) by new dipeptidyl-peptidase IV (CD26) inhibitors. 927 76

Evidence exists that the human immunodeficiency virus-1 (HIV-1) transactivator Tat occurs extracellularly and is involved in the immunosuppression of non-HIV-1-infected T cells of acquired immunodeficiency syndrome (AIDS) patients. The mechanism of this immunosuppressive activity of Tat has been controversially discussed. Interestingly, Tat binds to the T cell activation marker CD26, which has been shown to play a key role in the regulation of growth of lymphocytes and to inhibit its dipeptidyl peptidase IV (DP IV) activity. Here we show that the N-terminal nonapeptide MDPVDPNIE of Tat is a competitive inhibitor of DP IV and suppresses DNA synthesis of tetanus toxoid-stimulated peripheral blood mononuclear cells. Amino acid exchanges at positions 5 and 6 strongly weaken these effects. 1H nuclear magnetic resonance and molecular dynamics simulations of Tat(1-9), I5-Tat(1-9), and L6-Tat(1-9) suggest a similar backbone conformation for Tat(1-9) and L6-Tat(1-9). The solution conformation of I5-Tat(1-9) considerably differs from the other two. However, Tat(1-9) fits into our previously proposed active site model of DP IV in contrast to I5-Tat(1-9) and L6-Tat(1-9). Conformational alterations with regard to the parent peptide and spatial hindrances between these both compounds and DP IV can explain the loss of inhibitory activity. Our data suggest that the N-terminal residues of HIV-1 Tat do interact directly with the active site of DP IV and that DP IV does mediate Tat's immunosuppressive effects.
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PMID:The N-terminal structure of HIV-1 Tat is required for suppression of CD26-dependent T cell growth. 937 14

CD26 is a leukocyte activation marker that possesses dipeptidyl peptidase IV activity but whose natural substrates and immunological functions have not been clearly defined. Several chemo-kines, including RANTES (regulated on activation, normal T cell expressed and secreted), have now been shown to be substrates for recombinant soluble human CD26. The truncated RANTES(3-68) lacked the ability of native RANTES(1-68) to increase the cytosolic calcium concentration in human monocytes, but still induced this response in macrophages activated with macrophage colony-stimulating factor. Analysis of chemokine receptor messenger RNAs and patterns of desensitization of chemokine responses showed that the differential activity of the truncated molecule results from an altered receptor specificity. RANTES(3-68) showed a reduced activity, relative to that of RANTES(1-68), with cells expressing the recombinant CCR1 chemokine receptor, but retained the ability to stimulate CCR5 receptors and to inhibit the cytopathic effects of HIV-1. Our results indicate that CD26-mediated processing together with cell activation-induced changes in receptor expression provides an integrated mechanism for differential cell recruitment and for the regulation of target cell specificity of RANTES, and possibly other chemokines.
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PMID:Regulation of the receptor specificity and function of the chemokine RANTES (regulated on activation, normal T cell expressed and secreted) by dipeptidyl peptidase IV (CD26)-mediated cleavage. 938 85

Chemokines are key players in inflammation and infection. Natural forms of the C-X-C chemokine granulocyte chemotactic protein-2 (GCP-2) and the C-C chemokine regulated on activation normal T cell expressed and secreted (RANTES), which miss two NH2-terminal residues, including a Pro in the penultimate position, have been isolated from leukocytes or tumor cells. In chemotaxis and intracellular calcium mobilization assays, the truncation caused a reduction in the specific activity of RANTES but not of GCP-2. The serine protease CD26/dipeptidyl-peptidase IV (CD26/DPP IV) could induce this observed NH2-terminal truncation of GCP-2 and RANTES but not that of the monocyte chemotactic proteins MCP-1, MCP-2 and MCP-3. No significant difference in neutrophil activation was detected between intact and CD26/DPP IV-truncated GCP-2. In contrast to intact natural RANTES(1-68), which still chemoattracts monocytes at 10 ng/ml, CD26/DPP IV-truncated RANTES(3-68) was inactive at 300 ng/ml and behaved as a natural chemotaxis inhibitor. Compared with intact RANTES, only a 10-fold higher concentration of RANTES(3-68) induced a significant Ca2+ response. Furthermore, RANTES(3-68) inhibited infection of mononuclear cells by an M-tropic HIV-1 strain 5-fold more efficiently than intact RANTES. Thus, proteolytic processing of RANTES by CD26/DPP IV may constitute an important regulatory mechanism during anti-inflammatory and antiviral responses.
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PMID:Amino-terminal truncation of chemokines by CD26/dipeptidyl-peptidase IV. Conversion of RANTES into a potent inhibitor of monocyte chemotaxis and HIV-1-infection. 951 14

CD26 is a widely distributed 110 kD cell-surface glycoprotein with known dipeptidyl-peptidase IV (DPP-IV) activity in its extracellular domain. This ecto-enzyme is capable of cleaving amino terminal dipeptides from polypeptides with either L-proline or L-alanine in the penultimate position. On human T cells, CD26 expression appears late in thymic differentiation and is preferentially restricted to the CD4+ helper/memory population, and CD26 can deliver a potent co-stimulatory T-cell activation signal. The cDNA sequence of CD26 predicts a type II membrane protein with only 6 amino acids in its cytoplasmic region, suggesting that, in addition to DPP-IV enzyme activity, other signal-inducing molecules may be associated with CD26. Considerable evidence exists that CD26 interacts, presumably in its extracellular domain, with both CD45, a protein tyrosine phosphatase, and adenosine deaminase (ADA), each of which is capable of functioning in a signal transduction pathway. In addition, CD26 is the receptor for ADA, and ADA on the cell surface is involved in an important immunoregulatory mechanism by which released ADA binds to the cell-surface ADA. This multifunctional molecule may be involved in cell migration and the HIV-1-associated loss of CD4+ cells through the process of programmed cell death. Thus, CD26 appears to play a key role in a number of aspects of lymphocyte function.
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PMID:The structure and function of CD26 in the T-cell immune response. 955 64

CD26 is a leukocyte-activation antigen that is expressed on T lymphocytes and macrophages and possesses dipeptidyl peptidase IV (DPPIV) activity, whose natural substrates have not been identified yet. CXC chemokines, stromal cell-derived factor 1alpha (SDF-1alpha) and 1beta (SDF-1beta), sharing the receptor CXCR-4, are highly efficacious chemoattractants for resting lymphocytes and CD34(+) progenitor cells, and they efficiently block the CXCR-4-mediated entry into cells of T cell line tropic strains of HIV type 1 (HIV-1). Here we show that both the chemotactic and antiviral activities of these chemokines are abrogated by DPPIV-mediated specific removal of the N-terminal dipeptide, not only when the chemokines are produced in transformed mouse L cell line to express human CD26 but also when they were exposed to a human T cell line (H9) physiologically expressing CD26. Mutagenesis of SDF-1alpha confirmed the critical requirement of the N-terminal dipeptide for its chemotactic and antiviral activities. These data suggest that CD26-mediated cleavage of SDF-1alpha and SDF-1beta likely occurs in human bodies and promotes HIV-1 replication and disease progression. They may also explain why memory function of CD4(+) cells is preferentially lost in HIV-1 infection. Furthermore, CD26 would modulate various other biological processes in which SDF-1alpha and SDF-1beta are involved.
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PMID:Anti-HIV-1 and chemotactic activities of human stromal cell-derived factor 1alpha (SDF-1alpha) and SDF-1beta are abolished by CD26/dipeptidyl peptidase IV-mediated cleavage. 960 Sep 65

Stromal cell-derived factor 1alpha (SDF-1alpha) is a chemokine that has been shown to prevent infection of T-tropic HIV strains and is a possible substrate of CD26/dipeptidyl peptidase IV (DPPIV). In this study, we show that SDF-1alpha was cleaved at the N-terminal region by CD26/DPPIV and as a result the inhibitory activity of SDF-1alpha against HIV infection disappeared. Moreover, the chemotactic activity of SDF-1alpha also disappeared specifically by DPPIV activity of recombinant soluble CD26. These results suggested that dissemination of T-tropic HIV strains in vivo may be facilitated by CD26/DPPIV via inactivation of functional SDF-1alpha.
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PMID:Negative regulation of the anti-human immunodeficiency virus and chemotactic activity of human stromal cell-derived factor 1alpha by CD26/dipeptidyl peptidase IV. 970 10

The chemokine stromal-cell-derived factor-1alpha (SDF-1alpha) chemoattracts lymphocytes and CD34+ haematopoietic progenitors and is the ligand for CXCR4 (CXC chemokine receptor 4), the main co-receptor for T-tropic HIV-1 strains. SDF-1alpha was NH2-terminally cleaved to SDF-1alpha(3-68) by dipeptidyl-peptidase IV (CD26/DPP IV), which is present in blood in soluble and membrane-bound form. SDF-1alpha(3-68) lost both lymphocyte chemotactic and CXCR4-signaling properties. However, SDF-1alpha(3-68) still desensitized the SDF-1alpha(1-68)-induced Ca2+ response. In contrast to CD26/DPP IV-processed RANTES(3-68), SDF-1alpha(3-68) had diminished potency to inhibit HIV-1 infection. Thus, CD26/DPP IV impairs the inflammatory and haematopoietic potency of chemokines but plays a dual role in AIDS.
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PMID:Processing by CD26/dipeptidyl-peptidase IV reduces the chemotactic and anti-HIV-1 activity of stromal-cell-derived factor-1alpha. 971 Feb 54


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