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)

Glycolipid compositions of cells infected by human retroviruses (human immunodeficiency virus, HIV and/or human T-cell lymphotropic virus type I, HTLV-I) have been studied. Eight cell lines, comprising two HTLV-I-infected T-cell lines (MT-2 and MT-4), two HTLV-I-negative T-cell lines (Jurkat and MF), a macrophage cell line (U937), and three HIV-infected counterpart cell lines (MT-4/HIV, Jurkat/HIV and U937/HIV) were used. The neutral glycolipids and gangliosides isolated from these cell lines were compared. Among them, the HTLV-I-infected T-cell lines, MT-2 and MT-4, showed similar patterns for both neutral glycolipids and gangliosides. Neutral glycolipids (GlcCer and LacCer) of MT-2 and MT-4 cells were markedly decreased, and a ganglioside, GM3, of theirs was decreased to only a trace amount compared to that in other cell lines. Gangliosides of MT-4 and MT-4/HIV were further separated on an Iatrobeads column, and were identified as GM2, GM1a and GD1a by methylation and liquid secondary ion mass spectrometric analyses. Since the patterns of neutral glycolipids and gangliosides of MT-2 and MT-4 are unique, as compared to those of HTLV-I-negative cells, it is suggested that these changes are related to HTLV-1 infection. No prominent differences in the ganglioside compositions between HIV-infected and non-infected cell lines could be observed. But it is noteworthy that the contents of asialo-GM2 in Jurkat/HIV and MT-4/HIV cells were increased as compared to those in the parental cell lines.
 ...
PMID:Glycosphingolipid compositions of human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV)-infected cell lines. 850 47

In HIV-1 infection, the appearance of syncytia-inducing (SI) isolates is associated with a more rapid decline of CD4+ cells and progression to AIDS. Agents that inhibit either virus infection or syncytia formation have the potential to be therapeutically useful. Lipophosphoglycan (LPG), the major glycoconjugate of Leishmania, was recently shown to be a potent nonspecific inhibitor of viral membrane fusion. In this study, LPG demonstrated a dose-dependent inhibition of HIV-1-induced syncytia formation in CD4+ MT-2 cells infected with distinct SI isolates. Fragments of LPG were used to show that inhibition of syncytia formation was dependent on the length of the LPG fragment. Treatment of CD4+ cells or HIV-1 isolates with LPG inhibited infection in vitro. Furthermore, LPG inhibited the replication of SI viral isolates in CD4+ T cells in vitro. LPG had no toxic effects on peripheral blood mononuclear cells at the highest concentrations used in these assays. Further, LPG rapidly associated with the surface membrane of a human T cell line and subsequently disassociated over a 24-h period. The development of compounds capable of inhibiting HIV-induced syncytia formation should provide novel therapeutic approaches to control the spread of virus and disease progression.
 ...
PMID:Inhibition of HIV-1-induced syncytia formation and infectivity by lipophosphoglycan from Leishmania. 854 28

The roles of the CD4 receptor and the src kinase p56lck were examined in the process of HIV-induced apoptosis of CD4+ T lymphocytes. The presence of the CD4 cytoplasmic tail was found to be essential in delivering an apoptotic signal, and interaction of CD4 with p56lck potentiated HIV-induced apoptosis. Apoptosis, but not HIV replication, was abrogated by deleting the NH2-terminal intracytoplasmic tail of CD4, or by mutating the two critical cysteines in this tail that are responsible for CD4-p56lck interaction. Introduction of p56lck in C8166-45 or MT-2 cells, CD4+ T cell lines deficient for this protein, greatly increased HIV-induced apoptosis and syncytium formation. The ability of p56lck to deliver an apoptotic signal did not depend on its kinase function, since a kinase-deficient mutant was as effective as its normal counterpart in inducing apoptosis, suggesting that p56lck may act as an adapter to anchor other proteins to transduce the death signal.
 ...
PMID:HIV-induced apoptosis requires the CD4 receptor cytoplasmic tail and is accelerated by interaction of CD4 with p56lck. 855 Dec 42

The prevalence of HIV-1 sequences of the envelope domains V1V2 and V3 was analyzed by RT-PCR amplification. Two distinct biological phenotypes of HIV-1 have been described: the nonsyncytium-inducing (NSI) phenotype, best characterized by the inability to infect MT-2 cells, and the syncytium-inducing phenotype (SI), with the ability to infect MT-2 cells. Viral phenotype SI has been associated with HIV pathogenesis. The presence of positively charged amino acids at position 306 and 320 in the V3 domain of gp120 has been shown to be required for the support of the SI phenotype. In addition, V2 elongation and relocation of N-glycosylation sites were postulated to herald an NSI to SI phenotype switch. The present study was designed to assess the stability of an elongated V2 region with relocated N-glycosylation sites observed in SI isolates compared to NSI isolates. Eleven isolates with the SI phenotype and 19 isolates with the NSI phenotype were included in the study. Nine of the SI and 1 of the NSI isolates had a positively charged residue at position 306 or 320 (p < 0.001) in the V3 domain as assessed by direct sequencing of the viral RNA. In contrast, elongation and/or relocation of N-glycosylation sites of the V2 variable region were not found to be a consistent genetic feature of the SI phenotype. However, SI isolates had more positively charged amino acid residues in the hypervariable V2 region compared with NSI isolates. In one of the two SI isolates lacking positively charged amino acids at positions 306 or 320 in the V3 loop an elongation of 26 amino acids with 4 additional N-linked glycosylation sites was observed in the V2 region. This is consistent with the theory that elongation of V2 may be transiently required for SI conversion. These results suggest that maintenance of the SI phenotype requires positively charged amino acids in V3 in the majority of the virus population, but not an elongated V2 region with added or relocated N-linked glycosylation sites. Although increased charged residues in the V2 region may contribute.
 ...
PMID:Maintenance of syncytium-inducing phenotype of HIV type 1 is associated with positively charged residues in the HIV type 1 gp120 V2 domain without fixed positions, elongation, or relocated N-linked glycosylation sites. 857 72

Humic acids are natural constituents of soil and ground water and mainly consist of mixtures of polycyclic phenolic compounds. A similar complex of compounds with a mean size of about 1000 Da, designated HS-1500, was synthesized by oxidation of hydroquinone. HS-1500 inhibited HIV-1 infection of MT-2 cells with an IC50 of 50-300 ng/ml and showed a mean cell toxicity of about 600 micrograms/ml. Inhibition of HIV-induced syncytium formation was observed at 10-50 micrograms/ml. Treatment of free and cell-attached HIV with HS-1500 irreversibly reduced its infectivity, whereas the susceptibility of target cells for the virus was not impaired by treatment prior to infection. The HIV envelope protein gp120SU bound to sepharose-coupled HS-1500 and could be eluted by high salt and detergent. HS-1500 interfered with the CD4-induced proteolytic cleavage of the V3 loop of virion gp120SU. Furthermore, binding of V3 loop-specific antibodies was irreversibly inhibited, whereas binding of soluble CD4 to gp120SU on virus and infected cells was not affected. In conclusion, our data suggest, that the synthetic humic acid analogue inhibits the infectivity of HIV particles by interference with a V3 loop-mediated step of virus entry.
 ...
PMID:Inhibition of HIV-1 in cell culture by synthetic humate analogues derived from hydroquinone: mechanism of inhibition. 861 Apr 66

We have isolated a new variant of HIV-1 from Nigeria, Africa. The virus was recovered from the peripheral blood mononuclear cells (PBMCs) of an apparently healthy 23-year-old male from Ibadan, Nigeria. The in vitro studies indicated that the virus was highly cytopathic and replicated well in normal PBMCs, established T-cell lines and the monocytic cell line U937. The highest replicative titre of the virus was obtained in freshly isolated primary macrophage/monocyte cells which also showed the least cytopathology. Most other cultures showed single-cell cytolysis and giant cells, and syncytia were not induced in the HTLV-1 infected MT-2 cells. Since no HIV strain has been isolated from Nigeria, we obtained cDNA clones containing the env gene, to further characterize the Nigerian virus. Based on the DNA sequence analysis of 14 clones containing the coding region for its gp 120 protein, the Nigerian HIV isolate has been classified as HIV-1 subtype A. Only one subtype A virus from Rwanda has been characterized and this virus has not been shown to exhibit extreme cytopathicity in various cell types as was observed with the Nigerian strain. Further, the ability of this virus to grow well in lymphocytes, monocytes and macrophages and to exhibit cytopathicity without causing syncytia are uncommon properties distinguishing the Nigerian virus from other HIV-1 strains. Since most macrophage-tropic viruses have been associated with 'neurotropism', the isolation of an HIV-1 strain from the blood of an individual with no known neurological disorder indicates that this rapidly replicating cytopathic virus, with a broad host range, may play an important role in the pathogenesis of HIV disease. This represents the first report of an HIV-1 isolate from Nigeria.
 ...
PMID:Isolation and characterization of a new subtype A variant of human immunodeficiency virus type I from Nigeria. 867 28

Plants are a rich source of anti-viral substances. The National Cancer Institute therefore annually screens about 1500 species from Africa, Southeast Asia, and South and Central America, but not Bolivia, for anti-HIV activity. Several unique compounds with anti-HIV activity have emerged from the program. The Kallawaya Indians of Bolivia follow a medical tradition from the Tiahuanaco (400-1145), Mollo (1145-1435), Inca (1438-1532), Spanish (1532-1825), and Bolivian Republic (from 1825) which is only recently starting to be reported. They use approximately 900 of the more than 2000 medicinal plants found across Bolivia. Aqueous, organic, and alcoholic extracts of more than 100 samples of 60 species of Kallawaya medicinal herbs representing 30 plant families were assayed to compare their toxicity and ability to protect MT-2 T-lymphoblastoid cells from the cytopathic effects of HIV. The therapeutic index (TI) of sampled species is defined as the ratio of anti-HIV activity to toxic concentration. A TI of greater than 25 was chosen as the prerequisite for future bioassay-directed isolation of the active components as leads for potential new anti-HIV drugs. TI was greater than 25 for 18 species, including seven greater than 50 and one greater than 100. The anti-HIV activity resided mainly in the aqueous extracts and was concentrated in plants used in ethnomedicine to treat lung and liver diseases.
 ...
PMID:Drug leads from the Kallawaya herbalists of Bolivia. 1. Background, rationale, protocol and anti-HIV activity. 869 50

The therapeutic utility of a human immunodeficiency virus type 1 (HIV-1) protease inhibitor may depend on its intracellular concentration, which is a property of its uptake, metabolism, and/or efflux. Previous studies in our laboratory indicated that the addition of alpha 1 acid glycoprotein (alpha 1 AGP) to the medium markedly increased the amount of the drug required to limit infection in vitro. In this study, physiologically relevant concentrations of alpha 1 AGP and a radiolabeled inhibitor, A-80987, were used to determine both the uptake and activity of the agent in HIV-1-infected human peripheral blood mononuclear cells and cell lines. Both the uptake and efflux of 14C-labeled A-80987 were rapid (t1/2, < 5 min). Uptake of the drug was linearly dependent on the concentration but insensitive to the metabolic inhibitors KF, sodium cyanide, or CCCP (carbonyl cyanide m-chlorophenyl hydrazone). The amount of A-80987 which entered the cells was inversely proportional to the concentration of alpha 1 AGP (r2, 0.99) and directly proportional to the amount of extracellular non-protein-bound drug (r2, 0.99). Most importantly, the antiviral activity of the drug in HIV-1-infected peripheral blood mononuclear cells and MT-2 cells was directly related to the amount of intracellular A-80987. This study demonstrates that A-80987 binds to alpha 1 AGP, resulting in a free fraction below 10%. Cellular uptake of A-80987 is proportionally decreased in the presence of alpha 1 AGP, which results in less-than-expected antiviral activity. Importantly, we demonstrate for the first time that the inhibition of HIV protease is highly correlated with the amount of intracellular inhibitor.
 ...
PMID:Human serum alpha 1 acid glycoprotein reduces uptake, intracellular concentration, and antiviral activity of A-80987, an inhibitor of the human immunodeficiency virus type 1 protease. 872 25

The effect of antiretroviral treatment on HIV-1 phenotype was studied in a group of 83 nucleoside-naive patients. These initially nonsyncytium-inducing HIV-1 positive patients were followed prospectively for their HIV-1 phenotype. Syncytium-inducing variants were detected by cocultivation of peripheral blood mononuclear cells with the MT-2 T-cell line. Overall, 16 of 83 (19%) patients underwent a shift to syncytium-inducing phenotype: 11 of 67 during zidovudine treatment, 3 of 10 during zidovudine plus alpha interferon treatment, and 2 of 6 under initial zidovudine plus didanosine therapy. The results of this study demonstrate that neither zidovudine therapy alone nor combined with interferon or didanosine prevents the acquisition of syncytium-inducing strains.
 ...
PMID:Acquisition of syncytium-inducing HIV-1 strains during therapy with zidovudine alone or combined with alpha interferon or didanosine. 878 84

The culture of primary HIV isolates requires fresh phytohemagglutinin (PHA) stimulated peripheral blood mononuclear cells (PBMC) from seronegative donors. The variation inherent in donor cells, obtained from many different individuals, might affect the likelihood of virus isolation. We developed a quality control (QC) procedure which could determine quantitatively the susceptibility of random donor cells to HIV infection. The QC reagents consisted of cells and supernatants infected with a syncytium-inducing clinical isolate of HIV. Six 5-fold dilutions of QC cells (starting at 1000 cells) and supernatant (starting at a 1:200 dilution) were cultured in parallel with 1 x 10(6) 2-3-day-old PHA stimulated donor cells. After 7 or 14 days the resulting culture supernatant was tested for syncytia formation with MT-2 cells. A total of 127 sequential donors were tested over an 11 month period. All but one donor PBMC preparation was capable of being infected by the QC reagents (and this particular donor was permissive for several other primary isolates). The standard variation observed among all cultures was about one 5-fold dilution. The coefficient of variation ranged from 10.7 to 17.3%. These results suggest that the mononuclear cells from most, if not all, individuals are permissive for HIV to approximately the same level. Other quality control measures used in the laboratory are described.
 ...
PMID:Quality control of HIV cultures in a clinical retrovirology laboratory. 878 54


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