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

Four flavonoids (i.e., baicalein, quercetin, quercetagetin, and myricetin), known to be inhibitors of HIV-reverse transcriptase, have been shown to be more or less inhibitory to the activities of various cellular DNA and RNA polymerases. The degree of the inhibition varied depending on the combination of the flavonoid and the enzyme species: baicalein was moderately inhibitory to DNA polymerase gamma and E. coli DNA polymerase I; quercetin was strongly inhibitory to DNA polymerase beta and E. coli RNA polymerase and moderately inhibitory to DNA polymerase I; quercetagetin was a potent inhibitor for all of DNA polymerases alpha, beta, gamma, and I and RNA polymerase; myricetin was a strong inhibitor of DNA polymerases alpha and I and RNA polymerase. However, terminal deoxynucleotidyltransferase was virtually insensitive to inhibition by these flavonoids. The inhibition by the flavonoids was due to competition with the template.primer in the case of the DNA polymerases, whereas the inhibition was due to competition with the triphosphate substrate (GTP) in the case of RNA polymerase. The Ki values of these flavonoid inhibitors for DNA and RNA polymerases was determined.
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PMID:Mechanisms of inhibition of various cellular DNA and RNA polymerases by several flavonoids. 229 90

Serum neopterin is a metabolite of dihydroneopterin triphosphate, which is produced from GTP during immune activation. A study was undertaken in homosexual male subjects followed at 6 month intervals for 3 or more years to determine the value of serum neopterin changes induced by HIV infection. The significance of serum neopterin levels in evaluating prognosis of HIV-infected individuals was also assessed. Serum neopterin was found to be a useful indicator of the presence of HIV infection. Stratification of 29 HIV seroconverters showed a strong inverse correlation between the serum neopterin rise and the blood CD4 T cell fall in the first year following HIV infection. Thus, a small increase in neopterin (less than 5 nmol/L) at the time of HIV seroconversion was associated with minimal CD4 T cell reduction and a large increase (greater than 12 nmol/L) was associated with a much greater CD4 T cell fall. Neopterin levels were markedly different (lower) in individuals with little or no CD4 T cell fall when compared with those with moderate or marked rates of T cell fall. This relationship between serum neopterin and the CD4 T cell level was further confirmed by an evaluation of both parameters in a group of 799 seropositive homosexual men. In this analysis, serum neopterin was shown to have a significant predictive value for the development of AIDS within 3 years. Furthermore, when serum neopterin and CD4 T cell measurements were considered together, the prognostic value of the combination was significantly greater than either alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum neopterin changes in HIV-infected subjects: indicator of significant pathology, CD4 T cell changes, and the development of AIDS. 278 72

Apart from the retroviral gag, pol and env the HIV genome contains the F (3' orf) gene which encodes a polypeptide of 206 amino acids which is myristylated at the N-terminal and whose function is unknown. We have expressed the F gene in Escherichia coli and from a recombinant vaccinia virus, VVTGfHIV. The F-protein produced in VVTGfHIV-infected mammalian cells is myristilated, and is phosphorylated by protein kinase C at a residue close to the N-terminus like pp60-src (ref. 5). Purified bacterial F-protein also shows the GTPase, autophosphorylation and GTP-binding activities reported for the ras gene product. Furthermore, we show that expression of F in a CD4+ cell line down-regulates the CD4(T4) antigen. These results suggest that F is important in the pathophysiology of AIDS (acquired immune deficiency syndrome).
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PMID:HIV F/3' orf encodes a phosphorylated GTP-binding protein resembling an oncogene product. 311 20

Three hundred and two intravenous drug addicts (IVDA) from five towns in Northeastern Italy were studied. Of the males, 37/249 (14.8%) were homosexuals and of the females, 29/53 (54.7%) were prostitutes; 118 (39.0%) were alcoholics. AST levels were abnormal in 31.8%, ALT in 45.7%, GTP in 36.4%, and bilirubin in 14.6%. The prevalence of HBsAg (13.9%) and HBeAg (21.4% of HBsAg positive) was significantly higher than in 2,983 controls (4.2% and 6.3%, p less than .001 and p less than .02, respectively). Of the HBsAg positive subjects, 51.7% had anti-HDV antibodies. Among 260 HBsAg negative cases, 146 (56.2%) were anti-HBs and anti-HBc positive, 76 (29.2%) were anti-HBc positive and anti-HBs negative (25 anti-HBe positive and 51 anti-HBe negative), and 38 had no HBV markers. Anti-HIV ELISA positive subjects came to 70.5% (triplicate determination with absolute concordance) and Western blot analysis confirmed the results in 99.1% of ELISA positive and 100% of ELISA negative subjects. The prevalence of anti-HIV was significantly higher in anti-HBc positive than negative cases (p less than .02), even excluding HBsAg positive subjects. Cases negative for HIV and HBV had a significantly lower median duration of drug abuse than those with past or present infection (36 vs 60 months, p less than .001). HIV-related diseases were present in 56.3% of the cases (120/213; PGL in 94, ARC in 24, and AIDS in two).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HIV and HBV infection in intravenous drug addicts from northeastern Italy. 349 7

The Nucleic Acid Sequence-Based Amplification (NASBA) process involves alternate steps of DNA synthesis from an RNA template and RNA synthesis from a DNA template, using avian myeloblastosis virus (AMV) reverse transcriptase and T7 RNA polymerase, respectively. The overall fidelity of the amplification process was determined by sequence analysis of cloned DNA products of NASBA reactions. An error frequency of less than 0.3% was observed in cloned DNA products from two different segments of the HIV-1 gag gene. Partial substitution of GTP with ITP in the NASBA reaction did not significantly change the fidelity of the process. An error rate of 2 x 10(-4) was calculated for the combined effects of both polymerases.
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PMID:Fidelity of nucleic acid amplification with avian myeloblastosis virus reverse transcriptase and T7 RNA polymerase. 753 77

The role of the human immunodeficiency virus (HIV-1) Nef protein in T cell activation pathways was investigated using a Jurkat CD4+ cell line stably transfected with a Nef expression vector. Secretion of IL-2 and TNF-alpha, surface expression of IL-2R, and DNA-binding activity of NF-kappa B and AP-1 (Fos/Jun) complex in response to phorbol myristate acetate, TNF-alpha, or immobilized antibodies to CD3 were monitored. These parameters were not modified by Nef expression in Jurkat cells, whereas stimulation with the same stimuli resulted in partial inhibition of LTR activation in Nef+ Jurkat cells. This inhibition was not mediated through Nef phosphorylation on Thr-15 or GTP-binding activity because mutations in critical sites did not alter this inhibition. Analysis of truncated LTRs confirmed that inhibition of LTR activation was not mediated through NF-kappa B-binding activity but through the region containing the negative responding elements (NREs). These results suggest that Nef downmodulates LTR activation without significantly inhibiting the capacity of T cells to respond to immunological activations.
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PMID:Role of HIV-1 Nef expression in activation pathways in CD4+ T cells. 791 14

We have previously described a rat mAb directed against a peptide derived from the vif protein of HIV-1 that recognized two Schistosoma mansoni (Sm) antigens with a major band at 65 kDa. Epitope mapping of this mAb using overlapping hexapeptides derived from the vif peptide revealed that the motif recognized was PLPSVT. The screening of a Sm cDNA library led to the identification of two clones, Sm70 and Sm65. The two deduced protein sequences did not share any common structural features apart from the epitope recognized by the mAb (see below), and did not show significant identity to sequences present in the data bases. However, the N terminus of the deduced sequence of the Sm70 protein exhibits a consensus sequence known to be an ATP/GTP binding site. Furthermore, the C terminus of the deduced Sm65 protein sequence was found to contain a conserved hexapeptide with a consensus sequence LPETGE reported to be an important motif of the surface proteins of gram-positive cocci. Both proteins exhibit a peptide sequence (PLRSVT for Sm70 and PVGSVT for Sm65) similar to the epitope recognized by the mAb anti-vif. Western blotting experiments showed that the mAb anti-vif reacted with both proteins. However, only Sm65 was recognized by sera from HIV-1-seropositive individuals, whereas both proteins were recognized by S. mansoni-infected patients.
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PMID:Molecular characterization of two Schistosoma mansoni proteins sharing common motifs with the vif protein of HIV-1. 805 9

Proliferative defects have been reported at the level of DNA synthesis, even in T-lymphocytes from asymptomatic human immunodeficiency virus type-1+ (HIV-1+) patients. Since purine and pyrimidine ribonucleotide availability is crucial for proliferation, we compared the ability of HIV-1- and HIV-1+ T-lymphocytes (> 95% CD4+ and CD8+) to activate de novo biosynthetic and salvage pathways following phytohemagglutinin stimulation using 14C-labeled precursors. The striking abnormality already detectable in asymptomatic patients' cells was the impaired ability of CTP, UDP-Glc, and UTP pools to expand over 72 h (44-70% of control), although ATP and GTP pools and responses were normal. In symptomatic patients, resting T-cells showed markedly reduced pyrimidine pools (53-74% of control) with no change following activation. Relatively normal ATP, GTP, and NAD pools masked the same impaired response of de novo synthesis to activation, with ATP and GTP being reduced by 50% at 48 h. Purine salvage was more active than the control in unstimulated HIV-1+ cells. This impaired de novo synthesis in HIV-1+ T-lymphocytes severely restricts the availability of ribonucleotides for vital growth-related activities such as membrane expansion and strand break repair as well as DNA and RNA synthesis. The data indicate that resting T-lymphocytes from symptomatic patients survive through enhanced salvage, but the stimulation induces metabolic cell death, and provide an explanation for the activation-associated lymphocyte death seen in HIV-1+ T-lymphocytes.
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PMID:T-lymphocytes from AIDS patients are unable to synthesize ribonucleotides de novo in response to mitogenic stimulation. Impaired pyrimidine responses are already evident at early stages of HIV-1 infection. 853 Mar 57

The understanding of early events in the expression of genes has vastly improved in recent years with the identification of a variety of gene- and sequence-specific DNA binding transcription factors. One such protein, Sp1, has been implicated in activating transcription of various cellular and viral genes including those of HIV, and SIV types of retroviruses. The basic recognition site for Sp1 has been identified as variants of a 10 base-pairs long GC-rich DNA, often containing a hexanucleotide segment 5'-GGGCGG (termed GC-box). However, variations in both the relative protein-DNA binding affinity and the nature of binding sequences have been noted. Two-dimensional 1H-NMR experiments (500 MHz) were employed for conformational studies of two decadeoxyribonucleotide duplexes, d(GAGGCGTGGC).d(GCCACGCCTC), termed Sp1-III, and d(GGGAGTGGCG).d(CGCCACTCCC), termed Sp1-I. These are two of the highest affinity Sp1 binding sites and consist of diverse positioning of the tri- and tetranucleotide segments GAG, GTG, GCG, GGCG, GTGG and GGAG, that occur frequently in other Sp1 binding sites as well, and may form specific contacts with the protein. Phase-sensitive nuclear Overhauser enhancement (2D-NOESY and MINSY) and correlation (COSY) spectra were obtained for the assignment of the exchangeable and nonexchangeable protons in a sequence-specific fashion. As a prelude to determination of the detailed solution structures of the selected sequences, numerous structural constraints were obtained from angle-dependent coupling constants and relative intensities of distance-dependent intra- and internucleotide NOEs. Overall, each duplex adopts a structure similar to B-DNA with predominantly C2'-endo/S-type sugar conformation and anti-glycosidic torsion angles. A selective disruption of sequential NOE connectivities at the GAG.CAC and GTG.CAC steps, irrespective of the flanking sequence, suggests that conformational changes at these sites may act as unique determinants of sequence specific recognition/binding of Sp1. Implications for a specific inhibition of Sp1-mediated transcription by minor groove binding class of drugs, designed to recognize GC-rich sequences, are also briefly discussed.
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PMID:Conformational characteristics of high affinity Sp1 binding enhancer elements of HIV-LTR by high resolution 2D-NMR. 882 36

We have studied the purine nucleotide metabolism in the following cell lines: a), H9 (continuous human T-cell line) and H9/HTLV-III (H9 cell line, infected with RT+ HIV-I virus); b), A3.01 (human lymphoblastoid cell line CD4+) and 8E51 (line A3.01 permanently transfected with RT-HIV-I virus). Purine metabolism was studied by evaluating the content of the most important ribonucleotides (AMP-GMP-IMP-NAD-ADP-GDP-ATP-GTP) and their ratios. We determined several differences between the cell lines before and after viral infection. All nucleotides except triphosphates were reduced in H9/HTLV-III with respect to H9 cells; in 8E51, however, triphosphates were markedly reduced, while monophosphates increased with respect to A3.01 uninfected cells. Also the ratios exhibited different behaviors, for example the total adenine nucleotides total guanine nucleotides ratio (sigma A/sigma G) was enhanced in H9/HTLV-III cells with respect to H9 and unaltered in 8E51 with respect to A3.01 cells. We may conclude that the HIV-I virus strongly influences the purine nucleotide metabolism of the host cells and that the changes are different when induced either by RT+ or RT- virus.
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PMID:Purine ribonucleotide content in infected HIV-RT+ and HIV-RT- lymphoblastoid cell lines. 888 73


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