Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The natural CC-chemokine RANTES(3-68), missing two NH2-terminal residues, has been isolated from leukocytes and tumor cells. The highly specific aminopeptidase dipeptidyl peptidase IV (DPP IV), also called CD26, was shown to be responsible for this NH2-terminal truncation of RANTES. Here it is reported that CD26/DPP IV treatment of RANTES enhances its anti-HIV-1 activity. RANTES(3-68) inhibited infection of PBMC by M-tropic HIV-1 strains ten-fold more efficiently than intact RANTES. This difference in antiviral potency between intact and truncated RANTES was even more pronounced (at least 25-fold) in CCR5-transfected cell lines. In HOS.CD4.CCR5 transfected cells, RANTES(1-68) had virtually no anti-HIV-1 activity (IC50 > 130 nM), whereas RANTES(3-68) was a potent inhibitor of HIV-1 replication (1C50: 5.5 nM). The anti-HIV-1 activity of RANTES(1-68) in the different cell types correlated with the expression of CD26. Moreover, the addition of soluble CD26 together with RANTES(1-68) significantly enhanced the antiviral activity of RANTES in HOS.CD4.CCR5 cells (IC50: 13 nM). These observations point to an important role of CD26-mediated processing of RANTES in inhibiting the replication of CCR5-binding HIV strains in HIV-infected persons and in preventing the development of AIDS.
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PMID:CD26-processed RANTES(3-68), but not intact RANTES, has potent anti-HIV-1 activity. 983 58

We previously reported that certain short gp120 V2 region peptides homologous to vasaoactive intestinal peptide (VIP), such as "peptide T," were potent inhibitors of gp120 binding, infectivity, and neurotoxicity. The present study shows that synthetic V2-region-derived peptides have potent intrinsic chemotaxis agonist activity for human monocytes and also act as antagonists of high-affinity (0.1 pM) gp120-mediated monocyte chemotaxis. Selectivity is shown in that peptide T is more potent at suppressing M-tropic than T-tropic gp120 chemotaxis. Peptide T was also able to suppress monocyte chemotaxis to MIP-1beta, a chemokine with selectivity for CCR5 chemokine receptors, while chemotaxis of the more promiscuous ligand RANTES was not inhibited, nor was chemotaxis mediated by SDF-1alpha. In order to determine if peptide T mediated its gp120 antagonistic effects via modulation of CCR5 receptors, RANTES chemotaxis was studied using a CCR5 receptor-transfected HOS cell line. In this case, RANTES chemotaxis was potently inhibited by V2-region-derived short peptides. Peptide T also partially suppressed (125)I-MIP1-beta binding to human monocytes, suggesting action at a subset of MIP1-beta receptors. The V2 region of gp120 thus contains a potent receptor binding domain and synthetic peptides derived from this region modulate CCR5 chemokine receptor chemotactic signaling caused by either gp120 or chemokine ligands. The results have therapeutic implications and may explain recent clinical improvements, in that HIV/gp120 actions at CCR5 receptors, such as occur in the brain or early infection, would be susceptible to peptide T inhibition.
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PMID:Peptide T blocks GP120/CCR5 chemokine receptor-mediated chemotaxis. 1052 88

We investigated the expression of different chemokines in the surnatants and inside the cells of four human osteosarcoma cell lines. HOS, U-2 OS, MG63 and Saos-2 cells were cultured for 24, 48, 72 hours both in basal conditions and after stimulus with TNF alpha. Human stromal cells were used as control. IL-8 and MCP-1 are present in higher concentration in the surnatants in contrast to RANTES which is present primarily inside the cells. IL-8 and MCP-1 are not totally expressed by all the human osteosarcoma cell lines in unstimulated conditions, but became detectable after TNF alpha treatment. In general, this cytokine stimulated the production and release of the three chemokines.
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PMID:Expression of different chemokines by human osteosarcoma cells in response to tumor necrosis factor-alpha. 1065 98

We constructed replication competent, attenuated, nef-deleted SHIV(89.6) that express the rhesus macaque chemokine genes MIP-1alpha, RANTES, or LTN from the nef region. The chemokine inserts were stable during several passages in CEMx174 cells and the viruses grew well in activated rhesus PBMC. Expression of virally encoded MIP-1alpha, RANTES, or LTN was detected in culture fluids from infected HOS CD4(+) CXCR4(+) cells, that were used because they have a low background production of these chemokines. The in vitro growth kinetics of all nef-deleted SHIV(89.6) were slower than the parental strain in both CEMx174 cells and rhesus PBMC. Rhesus macaques were susceptible to SHIV(89.6-MIP-1alpha), SHIV(89.6-RANTES), SHIV(89.6-LTN), and nef-deleted control SHIV(89.6-dLTN) infection via the intrarectal route using standard virus doses, and intact viruses were reisolated from infected animals throughout the interval of acute infection. SHIV expressing the chemokine genes MIP-1alpha, RANTES, or LTN may help determine the in vivo roles for these chemokines in modulating virus replication and disease.
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PMID:Simian/human immunodeficiency virus(89.6) expressing the chemokine genes MIP-1alpha, RANTES, or lymphotactin. 1272 87

The tat, rev, vpu, and env genes from the monocytotropic CCR5-dependent HIV-1 Ba-L isolate were substituted for homologous simian immunodeficiency virus (SIV) sequences in the SIV genome. The resultant SHIV (SHIV Ba-L) replicated in CCR5-positive PM-1 cells but not in CCR5-negative CEMX174 cells. Infection of HOS cells expressing different co-receptors showed SHIV Ba-L to be strictly CCR5-dependent. Infection of PM-1 cells and rhesus peripheral blood mononuclear cells (PBMCs) was highly sensitive to RANTES but not to SDF-1. Although SHIV Ba-L infected rhesus and pigtail macaques intravenously or rectally, plasma viremia was controlled after 3 weeks. After serial passage through 4 pigtails by blood and bone marrow transfer, virus from pigtail PBMCs had higher in vitro infectious titers on rhesus PBMCs and was efficiently transmitted vaginally in rhesus and cynomolgus macaques. Plasma viremia generally persisted longer than after infection with unpassaged virus but was eventually controlled with no significant decrease in CD4+ T-cell counts in peripheral blood. The envelope gene of SHIV Ba-L revealed a very little genetic drift during in vivo passage. SHIV Ba-L provides a potentially useful model for R5 HIV-1 infection of humans.
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PMID:Characterization of a simian human immunodeficiency virus encoding the envelope gene from the CCR5-tropic HIV-1 Ba-L. 1284 40