Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus type 2 (HIV-2) and the closely related simian immunodeficiency viruses (SIVs) frequently use the orphan receptor BOB/GPR15 in addition to the chemokine receptor CCR5 for efficient entry and replication. However, the role of BOB/GPR15 in replication and pathogenesis of HIV-2 and SIV in vivo is unclear. This study shows that a single amino acid substitution in the V3 loop of the pathogenic SIVmac239 clone, 321P-->S, impaired the ability to use BOB/GPR15 for entry and replication but had little effect on the ability to use CCR5. This envelope variant replicated with an efficiency comparable with the parental SIVmac239 isolate in rhesus macaques. Furthermore, the mutant genotype and phenotype remained stable even after the onset of immunodeficiency. These results suggest that this cofactor plays only a minor role for the pathogenicity of the HIV-2/SIVmac/SIVsm group of primate lentiviruses.
 ...
PMID:Co-receptor usage of BOB/GPR15 in addition to CCR5 has no significant effect on replication of simian immunodeficiency virus in vivo. 1051 8

The chemokine receptor CCR5 and to a lesser extent CCR2b and CCR3 have been shown to serve as coreceptors for HIV-1 entry into macrophages. Individuals that are homozygous for a defective CCR5 allele (DeltaCCR5) are highly, but not fully, resistant to infection with HIV-1. Here, we want to emphasize the importance of DeltaCCR5 in in vitro as well as in vivo studies. We provide data that suggest that CCR5 polymorphism may affect the onset of AIDS dementia complex in vivo and data that show that HIV-1 replication is influenced by the DeltaCCR5 allele in vitro. Knowing the CCR5 genotype of an individual will help to better interpret research results and may even provide new information about mechanisms of disease.
 ...
PMID:Potential role of CCR5 polymorphism in the development of AIDS dementia complex. 1057 35

Peptides mimicking chemokine receptor CCR5 were synthesized and their anti-HIV-1 activities evaluated. Prepared compounds, especially a sulfated derivatives, showed significant anti-HIV-1 activities. Furthermore, a hybrid molecule linked to an N-carbomethoxycarbonyl-prolyl-phenylalanine (CPF) moiety had a greater effect.
 ...
PMID:Synthesis of peptides mimicking chemokine receptor CCR5 and their inhibitory effects against HIV-1 infection. 1070 30

The intensity of expression of the chemokine receptor CCR5 is involved in in vitro cell infectability by human immunodeficiency virus (HIV)-1 R5 isolates. Because CCR5 expression varies among individuals, the hypothesis that this expression could determine virus load in HIV-1-infected persons was tested. The mean number of CCR5 molecules per cell was measured on peripheral blood CD4+ T lymphocytes (CCR5 density) from HIV-1-infected, asymptomatic, nontreated adults. There was a strong correlation between HIV RNA plasma level and CCR5 density (P=.009) that was independent of cell activation and was not due to an HIV-induced CCR5 up-regulation. These data are compatible with the hypothesis that CCR5 density is a key factor governing cell infectability and in vivo virus production and explain the protective effect of the Delta32CCR5 deletion, which results in low CCR5 expression. CCR5 density might be of critical predictive value in HIV infection.
 ...
PMID:CD4+ T cell surface CCR5 density as a determining factor of virus load in persons infected with human immunodeficiency virus type 1. 1097 36

HIV particles that use the chemokine receptor CXCR4 as a coreceptor for entry into cells (X4-HIV) inefficiently transmit infection across mucosal surfaces [1], despite their presence in seminal fluid and mucosal secretions from infected individuals [2] [3] [4]. In addition, although intestinal lymphocytes are susceptible to infection with either X4-HIV particles or particles that use the chemokine receptor CCR5 for viral entry (R5-HIV) during ex vivo culture [5], only systemic inoculation of R5-chimeric simian-HIV (S-HIV) results in a rapid loss of CD4(+) intestinal lymphocytes in macaques [6]. The mechanisms underlying the inefficient capacity of X4-HIV to transmit infection across mucosal surfaces and to infect intestinal lymphocytes in vivo have remained elusive. The CCR5 ligands RANTES, MIP-1alpha and MIP-1beta suppress infection by R5-HIV-1 particles via induction of CCR5 internalization, and individuals whose peripheral blood lymphocytes produce high levels of these chemokines are relatively resistant to infection [7] [8] [9]. Here, we show that the CXCR4 ligand stromal derived factor-1 (SDF-1) is constitutively expressed by mucosal epithelial cells at sites of HIV transmission and propagation. Furthermore, CXCR4 is selectively downmodulated on intestinal lymphocytes within the setting of prominent SDF-1 expression. We postulate that mucosally derived SDF-1 continuously downmodulates CXCR4 on resident HIV target cells, thereby reducing the transmission and propagation of X4-HIV at mucosal sites. Moreover, such a mechanism could contribute to the delayed emergence of X4 isolates, which predominantly occurs during the later stages of the HIV infection.
 ...
PMID:Constitutive expression of stromal derived factor-1 by mucosal epithelia and its role in HIV transmission and propagation. 1074 78

The chemokine receptor CCR5 contains seven transmembrane-spanning domains. It binds chemokines and acts as co-receptor for macrophage (m)-tropic (or R5) strains of HIV-1. Monoclonal antibodies (mAb) to CCR5, 3A9 and 5C7, were used for biopanning a nonapeptide cysteine (C)-constrained phage-displayed random peptide library to ascertain contact residues and define tertiary structures of possible epitopes on CCR5. Reactivity of antibodies with phagotopes was established by enzyme-linked immunosorbent assay (ELISA). mAb 3A9 identified a phagotope C-HASIYDFGS-C (3A9 / 1), and 5C7 most frequently identified C-PHWLRDLRV-C (5C7 / 1). Corresponding peptides were synthesized. Phagotopes and synthetic peptides reacted in ELISA with corresponding antibodies and synthetic peptides inhibited antibody binding to the phagotopes. Reactivity by immunofluorescence of 3A9 with CCR5 was strongly inhibited by the corresponding peptide. Both mAb 3A9 and 5C7 reacted similarly with phagotopes and the corresponding peptide selected by the alternative mAb. The sequences of peptide inserts of phagotopes could be aligned as mimotopes of the sequence of CCR5. For phage 3A9 / 1, the motif SIYD aligned to residues at the N terminus and FG to residues on the first extracellular loop; for 5C7 / 1, residues at the N terminus, first extracellular loop, and possibly the third extracellular loop could be aligned and so would contribute to the mimotope. The synthetic peptides corresponding to the isolated phagotopes showed a CD4-dependent reactivity with gp120 of a primary, m-tropic HIV-1 isolate. Thus reactivity of antibodies raised to CCR5 against phage-displayed peptides defined mimotopes that reflect binding sites for these antibodies and reveal a part of the gp120 binding sites on CCR5.
 ...
PMID:Monoclonal antibody screening of a phage-displayed random peptide library reveals mimotopes of chemokine receptor CCR5: implications for the tertiary structure of the receptor and for an N-terminal binding site for HIV-1 gp120. 1076 Aug 6

Chemokine receptors have recently been shown to mediate HIV-1 entry into cells. The chemokine receptor CCR5 plays a key role in this process. A 32-bp deletion within the coding region of the CCR5 gene generates a truncated nonfunctional receptor. In HIV-1-infected individuals homozygous for this mutation, disease progression is inhibited. We analyzed the frequencies of the deletion in HIV-1-infected seropositive individuals. No significant differences in allelic frequencies of the CCR5 gene between the control and general HIV-1-infected cohorts and within the latter group between the infected individuals and patients with AIDS symptoms were revealed.
 ...
PMID:[Analysis of the 32 bp deletion in the CCR5 chemokine receptor gene in people from Moscow, infected with HIV-1]. 1086 93

FPRL1 is a seven-transmembrane (STM), G-protein coupled receptor which was originally identified as a low affinity receptor for the bacterial chemotactic formyl peptide and a high affinity receptor for the lipid metabolite lipoxin A4. We recently discovered that a number of peptides, including several synthetic domains of the HIV-1 envelope proteins and the serum amyloid A, use FPRL1 to induce migration and calcium mobilization in human monocytes and neutrophils. In this study, we report that a synthetic peptide domain of the V3 region of the HIV-1 envelope gp120, activates the FPRL1 receptor in monocytes and neutrophils. Furthermore, monocytes prestimulated with V3 peptide showed reduced response to several chemokines that use multiple cell receptors. This is associated with a rapid phosphorylation of the chemokine receptor CCR5 on the serine residues. Our study suggests that FPRL1, as a classical chemoattractant receptor, may play an important role in modulating monocyte activation in the presence of multiple stimuli.
 ...
PMID:Activation of the chemotactic peptide receptor FPRL1 in monocytes phosphorylates the chemokine receptor CCR5 and attenuates cell responses to selected chemokines. 1087 39

The beta-chemokine receptor CCR5 is considered to be an attractive target for inhibition of CCR5-using (R5 or macrophage-tropic) HIV-1. However, R5 HIV-1 cannot replicate in CD4+ T cell or monocyte lines because of the lack of CCR5 expression on their surface, which apparently hampers discovery and development of effective CCR5 antagonists against HIV-1 replication. In this study, we have established the CCR5-expressing T cell line MOLT-4/CCR5, highly permissive to the replication of R5 HIV-1. The cells express a considerable amount of CCR5 on their surface. When the cells were infected with the R5 HIV-1 strains Ba-L and JR-FL, the virus-induced cytopathic effect (syncytium formation) was observed, and the cells produced large amounts of HIV-1 p24 antigen in the culture supernatants. The analyses of progeny viruses for their coreceptor use and gp120 V3 nucleotide sequence revealed that they were R5 HIV-1. The parental cell line MOLT-4 was much less susceptible to Ba-L and totally insusceptible to JR-FL. Furthermore, MOLT-4/CCR5 cells could support the replication of an R5 clinical isolate, but MOLT-4 cells could not. When TAK-779, a novel small-molecule nonpeptide CCR5 antagonist, was examined for its inhibitory effect on R5 HIV-1 replication in MOLT-4/CCR5 cells, the compound displayed potent antiviral activity, as demonstrated in peripheral blood mononuclear cells. These results indicate that the established cell line will be an extremely useful tool for experiments with R5 HIV-1.
 ...
PMID:Establishment of a CCR5-expressing T-lymphoblastoid cell line highly susceptible to R5 HIV type 1. 1089 Mar 54

The chemokine receptor CCR5 constitutes a major co-receptor for the R5 strains of HIV-1, and a mutant allele of the CCR5 gene, especially in the homozygous form delta32/delta32, confers resistance against infection by the virus. The frequency of the delta32 allele was determined in blood donors from 16 provinces, covering the entire territory of Poland. Among 861 individuals 182 (21.1%) were carriers of the mutated allele: 7 of them (0.8 %) were homozygotes delta32/delta32, and 175 (20.3%) were heterozygotes +/delta32, resulting in a 10.9% frequency of the delta32 allele. The highest frequencies of the mutated allele were found in the eastern and western provinces, and the lowest frequencies of the delta32 allele were detected in the provinces in the center of the country. This pattern of distribution may reflect the migration of the population from the eastern territories of Poland to the western part of the country after World War II.
 ...
PMID:Distribution of 32 alelle of the CCR5 gene in the population of Poland. 1104 7


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>