UMLS:C0019693 - FACTA Search

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

The nucleocapsid (NC) protein of human immunodeficiency virus HIV-1 (NCp7) is responsible for packaging the viral RNA by recognizing a packaging site (PSI) on the viral RNA genome. NCp7 is a molecule of 55 amino acids containing two zinc fingers, with only the first one being highly conserved among retroviruses. The first zinc finger is flanked by two basic amino acid clusters. Here we demonstrate that chemically synthesized NCp7 specifically binds to viral RNA containing the PSI using competitive filter binding assays. Deletion of the PSI from the RNA abrogates this effect. The 35 N-terminal amino acids of NCp7, comprising the first zinc finger, are sufficient for specific RNA binding. Chemically synthesized mutants of the first zinc finger demonstrate that the amino acid residues C-C-C/H-C/H are required for specific RNA binding and zinc coordination. Amino acid residues F16 and T24, but not K20, E21 and G22, located within this zinc finger, are essential for specific RNA binding as well. The second zinc finger cannot replace the first one. Furthermore, mutations in the basic amino acid residues flanking the first zinc finger demonstrate that R3, 7, 10, 29 and 32 but not K11, 14, 33 and 34 are also essential for specific binding. Specific binding to viral RNA is also observed with recombinant NCp15 and Pr55Gag. The results demonstrate for the first time specific interaction of a retroviral NC protein with its PSI RNA in vitro.
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PMID:Specific binding of HIV-1 nucleocapsid protein to PSI RNA in vitro requires N-terminal zinc finger and flanking basic amino acid residues. 815 90

Deficiency in antioxidant micronutrients have been observed in patients with AIDS. These observations concerning only some isolated nutrients demonstrate a defect in zinc, selenium, and glutathione. An increase in free radical production and lipid peroxidation has been also found in these patients, and takes a great importance with recent papers presenting an immunodeficiency and more important an increase in HIV-1 replication secondary to free radicals overproduction. We have assessed different studies, trying to obtain a global view of the antioxidant status of these patients. In adults we observe a progressive decrease for zinc, selenium, and vitamin E with the severity of disease, except that selenium remains normal at stage II. However, the main dramatic decrease concerns carotenoids whose level at stage II is only half the normal value. To understand if these decreases in antioxidant and increases in oxidative stress occur secondary to the aggravation of the disease or, conversely, are responsible for it, we undertook a longitudinal survey of asymptotic patients. The preliminary results of this evaluation are presented. Paradoxically, lipid peroxidation is higher at stage II than at stage IV. This may be consecutive to a more intense overproduction of oxygen free radicals by more viable polymorphonuclear (PMN) at the asymptomatic stage. The free radicals production and lipid peroxidation seem secondary to a direct induction by the virus of PMN stimulation and cytokines secretion. N-Acetyl cysteine or ascorbate have been demonstrated in cell culture to be capable of blocking the expression of HIV-1 after oxidative stress and N-acetyl cysteine inhibits in vitro TNF-induced apoptosis of infected cells. In regard to all these experimental data, few serious and large trials of antioxidants have been conducted in HIV-infected patients, although some preliminary studies using zinc or selenium have been performed. In our opinion it is now time to evaluate in humans the beneficial effect of antioxidants. The more promising candidates for presenting synergistic effects when associated with N-acetyl cysteine seem to be beta-carotene, selenium and zinc.
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PMID:Antioxidant status and lipid peroxidation in patients infected with HIV. 819 33

Recent studies indicate that multiple nutritional abnormalities occur relatively early in the course of human immunodeficiency virus (HIV-1) infection. Decreased plasma levels of vitamins B6, B12, A, and E and zinc have been correlated with dietary intake and associated with significant alterations in immune response and cognitive function. To determine the level of intake consistent with normal plasma nutrient levels, we examined nutrition status in relation to food consumption and nutrient supplementation in HIV-1-seropositive (HIV+) and -seronegative (HIV-) homosexual men. The mean level of total intake (diet plus supplements) for all nutrients was significantly higher in HIV+ men. To achieve normal plasma nutrient values, the HIV+ men appeared to require intake in multiples of the recommended dietary allowance (RDA) for vitamins A, E, B6, and B12 and zinc. For the HIV+ men, a relatively high proportion of biochemical deficiency was associated with consumption of vitamin B6 and zinc at the RDA level. Because little evidence of deficiency was observed with elevated intake in both groups, an effective program of nutritional supplementation may be beneficial in maintaining adequate plasma nutrient levels.
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PMID:Inadequate dietary intake and altered nutrition status in early HIV-1 infection. 819 17

The nucleocapsid protein NCp7 of the human immunodeficiency virus type I (HIV-1) is a 72 amino acid peptide containing two zinc fingers of the type CX2CX4HX4C linked by a short basic sequence 29RAPRKKG35. NCp7 was shown to activate in vitro both viral RNA dimerization and replication primer tRNA(Lys,3) annealing to the initiation site of reverse transcription. In order to clarify the possible structural role of the zinc fingers in the various functions of NCp7, complete sequence specific 1H NMR assignment of the entire protein was achieved by two-dimensional NMR experiments. Moreover, to characterize the role of the peptide linker in NCp7 folding, a synthetic analogue with an inversion of Pro31 configuration was studied by NMR and fluorescence techniques. Several long range NOEs implying amino acid protons from the folded zinc fingers and the spacer, such as Ala25 and Trp37, Phe16 and Trp37, Arg32 and Trp37, Lys33 and Trp37, Cys18 and Lys33 disappeared in the D-Pro31 (12-53)NCp7, confirming the spatial proximity of the two CCHC boxes observed in the (13-51)NCp7. This was also confirmed by iodide fluorescence quenching experiments. The N and C-terminal parts of NCp7 displayed a large flexibility except for two short sequences Tyr56 to Gly58 and Tyr64 to Gly66, which seemed to oscillate between random-coil and helical conformations. The biological relevance of the structural characteristics of NCp7 was studied in vitro and in vivo. Substitution of Pro31 by D-Pro31 in the active (13-64)NCp7 peptide led to a severe reduction of dimerization in vitro. Moreover, site-directed mutagenesis substituting Leu for Pro31 resulted in the formation of non-infectious and immature viral particles. These results suggest that the spatial proximity of the zinc fingers induced by the peptide linker, plays a critical role in encapsidation of genomic RNA and morphogenesis of HIV-1 infectious particles.
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PMID:Conformational behaviour of the active and inactive forms of the nucleocapsid NCp7 of HIV-1 studied by 1H NMR. 828 49

The V3 loop of the HIV (human immunodeficiency virus)-1 envelope glycoprotein gp120 likely plays a role in HIV-1 infectivity. Although the amino acid sequence of the V3 loop is hypervariable, it contains a conserved region, Gly-Pro-Gly-Arg, that shows similarity to the active-site Gly-Pro-Cys-Arg sequence of inter-alpha-trypsin and trypstatin proteinase inhibitors. The purpose of the present work was to identify proteinases recognizing substrates with basic amino acids in the P1 substrate site that are present in MOLT-4 cells, a human CD4-positive T helper lymphocyte cell line, and to characterize these enzymes in terms of substrate, pH and ionic-strength preferences, size and susceptibility to various inhibitors, including 24- and 36-amino-acid-long V3 loop peptides. Extraction of MOLT-4 cells at low ionic strength solubilized nearly all of the trypsin-like activity, which was separable into five peaks of activity by chromatography on Mono-Q: Peaks 1, 2a, 2b, 3 and 4. All showed a neutral pH optimum, and all except Peak 4 showed optimal activity at high ionic strength. Peak 1 preferred Tos-Gly-Pro-Arg, p-nitroanilide (-pNA) substrate; Peaks 2-4 preferred benzyloxycarbonyl-Val-Leu-Gly-Arg-pNA. Peak 1, a zinc-dependent enzyme with serine and histidine in the active site, exhibited an M(r) of 75,000 on Superose 12 and was poorly inhibited by V3 loop peptides. Peak 2 contained two overlapping peaks, called 2a and 2b, that exhibited properties of zinc-dependent metalloproteinases. Gel filtration of Peak 2 activities revealed a major peak of activity at 81 kDa and a shoulder centred at 240 kDa. Each was modestly inhibited by V3 loop peptides. Peak 3, a zinc-dependent proteinase, exhibited a molecular mass of 100 kDa by gel filtration and was particularly sensitive to inhibition by V3 loop peptides. Peak 4 exhibited a molecular mass of 1100 kDa by gel filtration and was not inhibited by V3 loop peptides. None of these enzymes could be classified as mast-cell tryptase, and material in MOLT-4 cells cross-reactive with anti-(human tryptase) antibodies was not detected. Whether any of the MOLT-4 proteinases described in this study play a role in HIV-1 infectivity remains to be examined.
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PMID:Separation and partial characterization of proteinases with substrate specificity for basic amino acids from human MOLT-4 T lymphocytes: identification of those inhibited by variable-loop-V3 peptides of HIV-1 (human immunodeficiency virus-1) envelope glycoprotein. 831 3

We have cloned and expressed HIV-1 gag p15 nucleocapsid protein (NCp15) in the form of a 41-kDa fusion polypeptide with glutathione-S-transferase (GST-NCp). The recombinant protein was rapidly degraded in bacterial lysates unless Zn2+ and Cd2+ were present in the extraction buffer. Inclusion of these metals stabilized the protein, allowing facile purification of GST-NCp by affinity chromatography. The native NCp15 was readily prepared from GST-NCp by proteolytic cleavage with thrombin. Both GST-NCp and the processed NCp15 were able to bind RNA containing sequences from the 5'-end of the HIV-1 genome. This binding was unaffected by the absence or the presence of Zn2+; however, the binding of RNA was absolutely dependent on the presence of K+. The GST-NCp fusion protein was nonselective in the binding of RNA, with all transcripts, including antisense and non-HIV RNA, binding with equal efficiency. In contrast, NCp15 was highly selective in binding of RNA. Sequences within nucleotides 1244-1412 of the HIV-1 proviral genome were found necessary for maximal binding of RNA to NCp15.
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PMID:Expression, purification, and RNA-binding properties of HIV-1 p15gag nucleocapsid protein. 837 99

In the virion core of retroviruses, the genomic RNA is tightly associated with nucleocapsid (NC) protein molecules, forming the nucleocapsid structure. NC protein, a highly basic protein with two zinc fingers, is indispensable for RNA dimerization, encapsidation and the initiation of reverse transcription in avian, murine and human retroviruses. Here we show that NC protein of HIV-1 (NCp7) and NCp7 mutants bind to DNA fragments representing proviral DNA sequences, forming stable complexes. NCp7 and NCp7 mutants form high molecular weight complexes with large DNA fragments and show cooperativity in binding to the DNAs. It appears that the conserved basic residues, and not the zinc fingers, are important for complex formation. In addition, NCp7 and several NCp7 mutants protect DNAs from nuclease digestion while the DNA ends appear to be poorly protected. NCp7 has been found to bind to strong stop cDNA, the initial product of reverse transcription, and to promote the annealing of this cDNA to HIV-1 RNA corresponding to the 3' end of the genome. In addition, NCp7 slightly stimulates an in vitro IN cleavage assay. These results indicate that the interactions between NCp7 and proviral DNA may be important during provirus synthesis and/or prior to integration.
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PMID:Interactions between HIV-1 nucleocapsid protein and viral DNA may have important functions in the viral life cycle. 838 40

FIV is a lentivirus infection of cats which induces an immunodeficiency syndrome associated with early qualitative defects in antigen-specific T cell function and with late quantitative defects in CD4+ T lymphocytes. We have observed that peripheral blood mononuclear cells (PBMC) from FIV-infected cats have impaired survival in culture. The mechanism of this in vitro dysfunction and depletion is not known. We have proposed that inappropriate induction of programmed cell death (apoptosis) could account for these in vitro defects. Here, we report that PBMC from FIV-infected cats, with impaired T cell blastogenesis and impaired survival in vitro, undergo an active cell death upon culture, which has the morphological and biochemical characteristics of programmed cell death (PCD). Apoptosis occurred in all six asymptomatic FIV-infected cats, and in none of the nine uninfected cats, which were studied. Changes in cell morphology under both light and electron microscopy, and fragmentation of genomic DNA were characteristic for apoptosing cells. Cell death was spontaneous and occurred in the absence of any stimuli, and culture with the T cell mitogen, concanavalin A (Con A), did not significantly enhance cell death. Activation-induced cell death was inhibited, in a dose-dependent manner, by addition to the incubation medium of zinc, which has been shown to inhibit the action of endonuclease responsible for the characteristic fragmentation of DNA. Since apoptosis has recently been implicated in AIDS pathogenesis, FIV infection may prove useful to study this aspect of retroviral, in particular HIV, infection.
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PMID:Programmed cell death (apoptosis) as a mechanism of cell death in peripheral blood mononuclear cells from cats infected with feline immunodeficiency virus (FIV). 839 41

There is an increased attention to preconception care and counseling (PCC) in the US. Midwives should include it into their practice. Even though the PCC concept is new, many midwives already know and/or practice its components, including risk assessment, health promotion, psychological and medical interventions, and follow-up. Opportunities for PCC are gynecology visits, postpartum visits, school-based programs, occupational health centers, and local health departments. Midwives can help women decide whether they are psychologically prepared for motherhood through group discussions and family-timing scenarios. They should refer women to substance abuse counseling and address physical abuse. A medical history and physical exam followed by an evaluation of any medical problems are also important. Preconception screening should include laboratory tests for hemoglobin or hematocrit, Rh factor, rubella titer, urine dipstick (protein and sugar), Pap smear, gonococcal culture, syphilis ...... and hepatitis B test. Midwives should offer women an illicit drug screen and an HIV serodiagnostic test. Additional tests recommended for some women include a tuberculosis screen, chlamydia culture or rapid screen, toxoplasmosis, herpes simplex, cytomegalovirus, varicella, hemoglobinopathies, Tay-Sachs, and karyotype. Factors which may affect sperm morphology are cigarette smoking, alcohol drinking, vitamins A and E, linoleic acid, and zinc. Other male factors which may affect pregnancy outcome are advanced age, sexually transmitted diseases, HIV, and exposure to drugs and chemicals. Midwives should determine the need to refer women for genetic counseling. They can help establish a positive environment for conception by conducting a nutritional history and counseling; promoting vitamin supplementation; by counseling about dangers of cigarette smoking, alcohol drinking, and drugs; and by keeping up to date on reproductive toxicology, environmental pollutants, and occupational hazards. Midwives should take a menstrual, contraceptive, and sexual history. Menstrual charting can help detect ovulation. Other issues needing to be addressed are infertility and choosing a care provider and birth place.
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PMID:Preconception care. An opportunity to maximize health in pregnancy. 841 Mar 47

The retroviral integrase (IN) protein is essential for integration of retroviral DNA into the host cell genome. To identify functional domains within the protein and to assess the importance of conserved residues, we performed site-directed mutagenesis of HIV-1 IN and analyzed the mutants in vitro for IN-mediated activities: 3' processing (att site-specific nuclease activity), strand transfer (the joining of att site oligonucleotides to target DNA), disintegration (the reverse of strand transfer), and integration site selection. Changing the conserved residue His-16 either to Cys or to Val in a proposed zinc-finger region had minimal effect on IN activities. Alteration of two highly conserved amino acid residues, Asp-116-->Ile and Glu-152-->Gly, each resulted in complete or nearly complete loss of 3' processing, strand transfer, and disintegration, whereas alteration of another conserved residue, Trp-235-->Glu, had no demonstrable effect on any of the activities in vitro. Two mutants, Asp-64-->Val and Arg-199-->Cys delta, each demonstrated differential effects on IN activities. Asp-64-->Val has no demonstrable strand transfer or disintegration activity yet maintains 3' processing activity at a diminished level. Arg-199-->Cys delta, which lacks part of the carboxyl terminus of IN, has impaired strand transfer activity without loss of disintegration activity. Use of a target site selection assay showed that all of our mutants with strand transfer activity maintain the same integration pattern as wild type IN. We conclude that not all highly conserved IN residues are essential for IN activities in vitro, zinc coordination by the proposed zinc-finger domain may not be required for the activities assayed, alteration of single residues can yield differential effects on IN activities, and target site selection into naked DNA is not necessarily altered by changes in strand transfer activity.
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PMID:Site-directed mutagenesis of HIV-1 integrase demonstrates differential effects on integrase functions in vitro. 842 Sep 82

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