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) displays several features which distinguish it from HIV-1. Among the differences in these two viruses are the responses of their enhancer regions to T-cell activation. For example, stimulation of HIV-1 transcription is largely dependent on two kappa B regulatory elements. In contrast, the HIV-2 enhancer has a single kappa B site and contains additional cis-acting sequences responsive to induction. One of these sites, previously termed CD3R, is a purine-rich site, also called PuB1, which is responsive to stimulation of the CD3 component of the T-cell receptor complex and binds Elf-1, a member of the ets proto-oncogene family. In this report, we examine the interaction of the PuB1 site with other sites in the HIV-2 enhancer. We demonstrate that the PuB1 site confers responsiveness to T-cell activators only in cooperation with additional enhancer elements. Induction of the HIV-2 enhancer is dependent on at least two other cis-acting regulatory elements in addition to PuB1 and kappa B. One of these elements is another purine-rich site (PuB2), which also binds recombinant Elf-1. An adjacent region, proximal to the PuB2 ets (pets) site, shows protection in DNase footprinting experiments with extracts from Jurkat T cells. Mutation of either the kappa B, PuB1, PuB2, or pets site significantly reduces the response of the HIV-2 enhancer to T-cell stimulation, an effect which is mediated at the RNA level. Therefore, activation of the HIV-2 enhancer is dependent on at least four cis-acting elements, only one of which is found in HIV-1, which act in synergy with one another. Despite their sequence similarity, the organization and function of the HIV-2 enhancer have diverged considerably from those of HIV-1.
 ...
PMID:Activation of the human immunodeficiency virus type 2 enhancer is dependent on purine box and kappa B regulatory elements. 150 Dec 84

HIV (human immunodeficiency virus) viraemia in serum or plasma of HIV-infected individuals was investigated by the polymerase chain reaction assay (PCR) in combination with reverse transcription to detect HIV-1 genomic RNA. Before PCR, plasma or serum was ultracentrifuged, precipitated virions were then treated with a RNase-free DNase, and a cDNA from the HIV-1 genomic RNA was synthesized. Thirty-three fresh plasma and seven sera from either HIV-1 antibody-positive individuals or patients treated with AZT were tested. Plasma from three patients were assayed 3 or 6 months apart. Twelve sera from HIV-1 antibody-negative individuals were used as negative control. PCR was performed with primers in LTR, gag and env regions: 11 of 40 samples were positive with three primer pairs, 16 with two primer pairs and 11 with only one primer pair. PCR on HIV-1 genomic cDNA was positive in 38 out of the 40 plasma or serum samples (95%), regardless of the clinical stage of the infection: HIV-1 was detected in 14 of the 15 untreated subjects and in 24 of the 25 AZT-treated patients. HIV p24 antigen was detected in the serum of 38% of subjects (15 of 40). The results suggest that this method is suitable for the detection of viral particles in plasma or serum from HIV-1-infected individuals irrespective of antiviral treatment.
 ...
PMID:The polymerase chain reaction for the detection of HIV-1 genomic RNA in plasma from infected individuals. 171 16

We have recently shown that phosphorothioate (PS) oligodeoxynucleotide (ODN) analogs, unlike their normal congeners, exhibit significant anti-HIV activity (Matsukura et al., (1987) Proc. Natl. Acad. Sci. USA 84, 7706-7710). We now report the syntheses, melting temperatures (Tm), and nuclease susceptibilities of a series of phosphorothioate ODN analogs. These include all-PS duplexes, duplexes with one normal chain and the other chain either all-PS, or end-capped with several PS groups at both 3' and 5' ends. The DNase susceptibilities of the S-ODNs are much less than the normal phosphodiesters, but by contrast duplexes of poly-rA with S-dT40 are much more susceptible to RNase H digestion. The Tm's for AT base pairs of S-ODNs are significantly depressed relative to normals, while GC base pairs show much less Tm depression. The Tm's of S-dT oligomers with poly-rA are reduced relative to the duplexes with normal dA oligomers. These results have significance for the biological properties of these analogs as anti-message inhibitors of gene expression, and provide a rational basis for the S-dC/G sequences as potential effective anti-AIDS agents.
 ...
PMID:Physicochemical properties of phosphorothioate oligodeoxynucleotides. 283 90

Interactions between HIV-1 and CMV may be important in the pathogenesis of AIDS. We have studied whether active CMV infection alters the cell tropism of HIV-1 in dually-infected individuals. Urines from HIV-seropositive individuals excreting CMV were compared to urines from CMV non-excretors. Sixty-six urines from HIV-seropositive individuals were tested. Infectious HIV-1 was not detected in any of the concentrated urines tested. The urines were filtered, concentrated, DNase-treated and cultured on HIV-1 non-permissive human forestin fibroblasts. HIV-1 DNA was detected by PCR with pol gene primers in 5 of 39 MRHF cell cultures inoculated with CMV culture positive urine (p = 0.037). HIV-1 DNA was not detected by PCR in uninfected fibroblasts, in fibroblasts inoculated with CMV uninfected urine from 27 HIV-seropositive patients or in fibroblasts cultured with 9 CMV culture positive urines from 16 HIV-seronegative renal transplant recipients. Supernatant fluid from an HIV-1 PCR-positive culture was passaged onto another fibroblast monolayer, and these cells were negative for HIV-1 DNA. Direct inoculation of fibroblasts with HIV-1 did not yield evidence of infection by PCR. CMV infection may facilitate HIV-1 DNA entry into ordinarily non-permissive cells.
 ...
PMID:HIV-1 DNA in fibroblast cultures infected with urine from HIV-seropositive cytomegalovirus (CMV) excretors. 760 3

Although a small amount of viral DNA has been shown to be enclosed within human immunodeficiency virus type 1 (HIV-1) virions, the majority of full-length viral DNA is formed after this virus infects target cells. Hence, we undertook investigations to identify the physical characteristics of the HIV-1 replication unit during the early events of infection. In these studies, nascent viral DNA synthesis was found to occur between 15 and 30 min after purified, DNase-treated HIV-1 virions were added to HUT 78 cells. At 1 h postinfection, a large amount of strong-stop viral DNA and some first-strand viral DNA had been synthesized. Several lines of evidence, including purification, nuclease digestion, and immunoprecipitation, indicated that these nascent viral DNAs were located within particles containing components such as reverse transcriptase and p24gag and gp120env proteins and having physical characteristics similar to those of intact virions.
 ...
PMID:Nascent human immunodeficiency virus type 1 reverse transcription occurs within an enveloped particle. 774 16

Variable levels of viral DNA have been demonstrated within human immunodeficiency virus type 1 (HIV-1) virions purified from cell cultures. In the present studies, it is demonstrated that DNase-resistant viral DNA is associated with HIV-1 virions purified from the peripheral blood plasma of both symptomatic and asymptomatic HIV-1-infected individuals. The differences in viral DNA copy numbers, detected by quantitative PCR in various regions of the HIV-1 genome, indicated that the intravirion HIV-1 DNA is frequently, but perhaps not totally, the result of partial reverse transcription. These in vivo data suggest that it may be valuable to further investigate the impact of virion-associated viral DNA upon the efficiency of intra- and interhost HIV-1 transmission modes.
 ...
PMID:Intravirion reverse transcripts in the peripheral blood plasma on human immunodeficiency virus type 1-infected individuals. 793 48

Extracellular HIV-1 virions purified from cell culture supernatants have been found to contain viral DNA that is the result of partial reverse transcription within the virus particles. Our data supported these observations and further indicated that the ratio of genomic RNA to viral DNA was approximately 10(3):1 for the "strong stop" (R-U5) region and 10(5):1 for the gag region. We have shown that, in the absence of detergent, large amounts of DNase-resistant viral DNA can be synthesized within intact HIV-1 virions, indicating that this phenomenon is not dependent on perturbation of the viral envelope. Nascent viral DNA synthesis also occurred in purified virions incubated at 37 degrees C in cell-free human physiological fluids including seminal plasma, blood plasma, breast milk, and fecal fluid. In vitro HIV-1 infection assays, in which HIV-1 DNA synthesis was initiated in HIV-1 virions by prior incubation with deoxyribonucleoside triphosphates, demonstrated that virus particles so treated had an increased infectious titer over untreated virions when incubated with target human T cells. Our data suggest that HIV-1 virion-associated DNA synthesis may occur in vivo and may impact on the efficiency of intra- and interhost virus transmission. If so, this phenomenon should prove to be an important target for antiviral therapeutic strategies.
 ...
PMID:Reverse transcription takes place within extracellular HIV-1 virions: potential biological significance. 814 46

Pharmacological modulation of the interaction between transcription factors and target DNA sequences of cellular and viral genes could have important effects in the experimental therapy of a large variety of human pathologies. For instance, alteration of the DNA/protein interaction might be among the molecular mechanisms of action of DNA-binding drugs, leading to an inhibition of the expression of genes involved in the control of in vitro and in vivo growth of neoplastic cells and virus DNA replication. Natural oligopeptides, such as distamycin, are powerful inhibitors of the interaction between nuclear factors and target DNA sequences and, therefore, have been proposed as compounds retaining antibiotic, antineoplastic and antiviral properties. In this study we performed DNAase I footprinting analysis using a PCR product mimicking a region of the long terminal repeat (LTR) of the human immunodeficiency type 1 (HIV-1) retrovirus. The data obtained suggest that distamycin binds to different regions of the HIV-1 LTR depending on the DNA sequence. Electrophoretic mobility shift assays using both crude nuclear extracts from the Jurkat T-lymphoid cell line and the recombinant proteins transcription factor IID and Sp1 suggest that distamycin differentially inhibits the interaction of these two proteins with their specific DNA target sequences, in good agreement with the results obtained by DNAase I footprinting analysis.
 ...
PMID:Sequence-specific recognition of the HIV-1 long terminal repeat by distamycin: a DNAase I footprinting study. 817 6

The human immunodeficiency virus (HIV-1) long terminal repeat (LTR) contains two binding sites for NF-kappa B in close proximity to three binding sites for the constitutive transcription factor, Sp1. Previously, stimulation of the HIV enhancer in response to mitogens has been attributed to the binding of NF-kappa B to the viral enhancer. In this report, we show that the binding of NF-kappa B is not by itself sufficient to induce HIV gene expression. Instead, a protein-protein interaction must occur between NF-kappa B and Sp1 bound to an adjacent site. Cooperativity both in DNA binding and in transcriptional activation of NF-kappa B and Sp1 was confirmed by electrophoretic mobility shift gel analysis, DNase footprinting, chemical cross-linking and transfection studies in vivo. With a heterologous promoter, we find that the interaction of NF-kappa B with Sp1 is dependent on orientation and position, and is not observed with other elements, including GATA, CCAAT or octamer. An increase in the spacing between the kappa B and Sp1 elements virtually abolishes this functional interaction, which is not restored when these sites are brought back into the same helical position. Several other promoters regulated by NF-kappa B also contain kappa B in proximity to Sp1 binding sites. These findings suggest that an interaction between NF-kappa B and Sp1 is required for inducible HIV-1 gene expression and may serve as a regulatory mechanism to activate specific viral and cellular genes.
 ...
PMID:A cooperative interaction between NF-kappa B and Sp1 is required for HIV-1 enhancer activation. 825 80

We found and isolated two natural products in the extract from a basidiomycete, Ganoderma lucidum, as eukaryotic DNA polymerase inhibitors. The compounds were identified as cerebrosides, (4E,8E)-N-D-2'-hydroxypalmitoyl- 1-O-beta-D-glucopyranosyl-9-methyl-4,8-sphingadienine and (4E,8E)-N-D-2'-hydroxystearoyl-1-O-beta-D-glucopyranos yl-9-methyl- 4,8-sphingadienine and were found to be identical to the mushroom fruiting body-inducing substances (FIS) reported. These cerebrosides selectively inhibited the activities of replicative DNA polymerases, especially the alpha-type, from phylogenetically broad eukaryotic species, whereas they hardly influenced the activities of DNA polymerase beta, prokaryotic DNA polymerases, terminal deoxynucleotidyl transferase, HIV reverse transcriptase, RNA polymerase, deoxyribonuclease I, and ATPase. The inhibition of another replicative polymerase, the delta-type, was moderate. The inhibitions of the replicative polymerases were dose-dependent, and the IC50 for animal or mushroom DNA polymerase alpha was achieved at approximately 12 micrograms/ml (16.2 microM) and for animal DNA polymerase delta at 57 micrograms/ml (77.2 microM). FIS is possibly a DNA polymerase inhibitor specific to the replicative enzyme group, and the fruiting body formation may be required for the suppression of the DNA replication or the vegetative growth of the mycelium.
 ...
PMID:A mushroom fruiting body-inducing substance inhibits activities of replicative DNA polymerases. 970 23


1 2 3 4 5 Next >>