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 replication of human immunodeficiency virus type 1 (HIV-1) requires cellular components to interact with regulatory elements located in the long terminal repeat (LTR) as well as viral proteins Tat and Rev. Several well known signaling transduction inhibitors were tested to determine their effects on the Tat-mediated transactivation using a transfection assay with the bacterial chloramphenicol acetyltransferase gene under the control of the HIV-1 LTR. The protein kinase C inhibitors curcumin and staurosporine, but not a tyrosine kinase inhibitor herbimycine A, inhibited Tat-mediated LTR-driven transactivation. Two antimalarial drugs quinacrine and chloroquine, that are also arachidonic acid metabolism inhibitors, were found to inhibit the Tat-mediated LTR-driven gene expression. Another inhibitor of arachidonic acid metabolism 4-bromophenacyl bromide was also found to inhibit Tat-mediated gene expression driven by HIV-1 LTR. However, the antimalarial drug quinine elicited no effects on Tat-mediated transactivation. These results suggest that the anti-arachidonic acid metabolism properties of quinacrine and chloroquine may be responsible for their ability to inhibit Tat-mediated LTR-regulated gene expression.
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PMID:Inhibition of HIV-1 Tat-mediated transactivation by quinacrine and chloroquine. 880 83

Eosinophils, when stimulated, release a variety of agents that can be toxic to ingested or extracellular targets. Among these systems is one that consists of eosinophil peroxidase (EPO), H2O2, and a halide. We report here that phorbol myristate acetate (PMA)-stimulated human eosinophils are virucidal to HIV-1 in a chloride-containing medium. When the eosinophil concentration is decreased to a level at which the virucidal effect is incomplete, the addition of bromide or iodide restored complete virucidal activity. The virucidal effect of eosinophils, PMA, and bromide under these conditions is inhibited by the peroxidase inhibitor azide and catalase, but not heated catalase or superoxide dismutase, implicating the EPO-H2O2-halide system. Purified EPO when combined with H2O2 in a chloride-containing medium is virucidal to HIV-1. When the EPO concentration is suboptimal, virucidal activity is increased by bromide, iodide, and, in this instance, thiocyanate and the virucidal activity of the bromide-supplemented system is inhibited by azide and catalase. Our findings, together with the demonstration that eosinophils express CD4 on their surface and, under some circumstances, can be productively infected with HIV-1, raise the possibility that biological oxidants formed by eosinophils can influence the pathogenesis of HIV-1 infection by their toxicity to eosinophil-associated or extracellular virus.
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PMID:Virucidal effect of stimulated eosinophils on human immunodeficiency virus type 1. 882 15

This study determined the frequency with which hepatitis C virus (HCV) could be detected in the saliva of 21 HCV-seropositive haemophiliac patients attending an Oral Surgery Unit. All sera were positive for HCV RNA by the polymerase chain reaction (PCR). Six of the patients were also HIV antibody positive. Saliva was collected both by spitting into a Universal container (whole saliva), and by means of Salivettes. Following RNA extraction from saliva specimens and synthesis of cDNA, nested PCR was performed. Amplified DNA was detected by agarose gel electrophoresis and ethidium bromide staining. Overall, HCV was detected in saliva from 10 of the subjects (8 HIV seronegative and 2 HIV seropositive) but there was not complete concordance between the Salivette specimens and normal whole saliva. Analysis of pellet and supernate fractions from whole saliva produced similar discrepancies. Repeat runs of PCR for HCV following freezing and thawing of the initially positive saliva specimens were unsuccessful. It was concluded that HCV is present in the saliva of some haemophiliac patients. However, careful optimisation of sample handling and storage methods and of PCR technique are required before the true prevalence of HCV shedding in saliva can be determined.
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PMID:Hepatitis C virus in saliva of haemophiliac patients attending an oral surgery unit. 886 Dec 92

A simple approach for the determination of drug susceptibilities by using human immunodeficiency virus type 1 (HIV-1) RNA from the sera of patients is described. HIV-1 RNA was extracted from patient sera, and the 5' part of the reverse transcriptase (RT) gene was transcribed into DNA and amplified in a nested PCR. The amplified fragment covers the 3' part of the protease gene and amino acids 1 to 304 of the RT gene. This fragment can be introduced through homologous recombination, as described previously, into a novel HIV-1 reference strain (pHXB2 delta 2-261RT) from which amino acids 2 to 261 of RT have been deleted. The resulting recombinant virus expresses all properties of the HXB2 reference strain except for those encoded by the introduced part of the patient RT gene. Recombinant viruses were subsequently tested for drug susceptibility in a microtiter format killing assay [3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay] as well as in the standard HeLa CD4+ plaque reduction assay. Similar susceptibility profiles were obtained by each assay with recombinant viruses derived from patients receiving alternating nevirapine and zidovudine treatment or lamivudine-zidovudine combination therapy. In conclusion, this approach enables high-through-put determination of the drug susceptibilities of serum RNA-derived RT genes, independent of the patient's viral background, and generates the possibility of relating changes in susceptibility to changes in viral genotypes.
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PMID:Human immunodeficiency virus type 1 drug susceptibility determination by using recombinant viruses generated from patient sera tested in a cell-killing assay. 889 Nov 52

Previously, we described two mutants of the cellular Rev co-factor, eukaryotic initiation factor 5A (eIF-5A M13 and M14), which suppress human immunodeficiency virus type 1 (HIV-1) SF2 replication in clonal T cell lines. This study introduced the notion that it is possible to develop gene therapies against infectious agents on the basis of mutant host factors required for viral replication. In this report, we provide further evidence to support this new paradigm and describe murine leukemia virus (MLV)-based retroviral vectors expressing three different eIF-5A mutants from the viral long terminal repeat (LTR). HIV-1 replication (SF2, HXB-3) was reduced up to 2 orders of magnitude in transduced, polyclonal T cell populations. All eIF-5A mutants also showed antiviral activity (approximately seven-fold reduction) in a chronic HIV-1 infection model. Expression of eIF-5A mutant M13 delta in peripheral blood lymphocytes (PBLs) showed no difference in proliferation and metabolic activity as determined in a 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT)-assay, suggesting that expression of this type of mutant protein is not associated with cellular toxicity. In summary, these data suggest that gene therapy for HIV-1 infection can be developed on the basis of mutants of the Rev co-factor eIF-5A.
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PMID:Intracellular expression of cellular eIF-5A mutants inhibits HIV-1 replication in human T cells: a feasibility study. 889 78

The simultaneous presence of multiple HIV-1 subtypes has become common in communities with the growth of the pandemic. As a consequence, the potentiality for an increased frequency of HIV-1 mixed infections caused by viruses of distinct subtypes could be expected. Thus, there is a need to estimate the prevalence and geographic distribution of infections caused by viruses of a singular subtype as well as coinfections caused by two or more HIV-1 strains of distinct subtypes. To address this need, we have developed a genetic method based on restriction fragment length polymorphism (RFLP) to screen for these two types of infections within infected populations. In this assay, restriction enzymes may be used to predict the phylogroup of HIV-1 infected samples. A 297 bp pol fragment spanning the entire viral protease gene and a 311 bp fragment of the p24 gag region are used for this analysis. The viral regions are amplified by nested PCR using DNA templates from uncultured peripheral blood mononuclear cells (PBMC) or virus culture. Classification of HIV-1 strains to well defined subtypes B, D, F, and A/C is done by sequential endonuclease restriction analysis of a PCR amplified-protease gene followed by analysis of the p24 gag region. The electrophoretic migration patterns visualized by ethidium bromide staining or by radiolabeled probes are then determined on a 10% polyacrylamide gel. In infections caused by viruses of a singular subtype, a single restriction pattern is detected, whereas in multiple infections caused by two or more viral strains of different subtypes, the combination of different digestion patterns are observed in infected individuals. Using this methodology we have screened for genetic variations in HIV-1 proviral DNA from thirty-three Brazilian samples. Our RFLP procedure classified thirty-two samples as single infections caused by viruses of subtypes B (31) and F (1), and one sample as dual infection caused by distinct viral strains. Subsequent sequence and phylogenetic analysis of the viral protease gene in lymphocytes of all these patients confirmed our RFLP findings in single infections, and demonstrated the existence of two distinct HIV-1 strains of subtypes F and D in a patient which lymphocytes showed the simultaneous presence of two different digestion patterns. As up to now, single infections caused by subtype D variants were not identified in Brazil, our data provide the first evidence of subtype D HIV-1 in this country. Because sequencing of HIV proviral DNA is not particularly practical for large-scale molecular epidemiological studies, the protease/gag-based RFLP screening method will be useful to predict the phylogroup of HIV-1, and to identify multiple infections caused by HIV-1 strains of distinct subtypes. We believe that this information is crucial for both evaluation of the HIV-1/AIDS pandemic and intervention strategies.
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PMID:Identification of single and dual infections with distinct subtypes of human immunodeficiency virus type 1 by using restriction fragment length polymorphism analysis. 893 82

Neutrophil (PMNL) function defects occur as a consequence of HIV infection. This study examined PMNL apoptosis in patients with the acquired immunodeficiency syndrome (AIDS) to determine if accelerated apoptosis contributes to impaired function. PMNL were isolated from 10 HIV-infected patients with CD4+ lymphocyte counts < 200/mm3 without signs of active infection and 7 healthy volunteers. PMNL were stained with acridine orange and ethidium bromide after 0, 3, 6, and 18 h in culture, and examined for the morphologic changes of apoptosis and viability by fluorescent microscopy. Apoptosis was also demonstrated by electron microscopy, flow cytometry, and DNA gel electrophoresis. Apoptosis was minimal at 0 h, but PMNL from AIDS patients exhibited significantly greater apoptosis than controls at 3 h (22.5+/-11.5 vs. 8.9+/-6.9%, P = 0.015), 6 h (38.1+/-14.2 vs. 18.1+/-4.5%, P = 0.003), and 18 h (71.3+/-19.0 vs. 38.8+/-16.7%, P = 0.002). Viabilities were > or = 88.0% for both groups from 0-6 h, but by 18 h viability was significantly decreased for the HIV group (58.8+/-12.4 vs. 83.5+/-10.4%, P = 0.001) due to an increase in non-viable apoptotic cells. Incubation with serum from AIDS patients had no effect on control PMNL, and incubation with control serum did not reduce the rate of apoptosis of PMNL from AIDS patients. Incubation with granulocyte colony-stimulating factor (G-CSF) in vitro significantly decreased apoptosis for PMNL from AIDS patients. PMNL from patients with AIDS exhibit markedly accelerated apoptosis ex vivo. In vivo, apoptosis and functional impairment of PMNL may contribute to the risk of secondary infections, and cytokine therapy may be of potential clinical benefit in this circumstance.
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PMID:Accelerated neutrophil apoptosis in the acquired immunodeficiency syndrome. 898 16

We have developed a microplate hybridization(MH) technique, which utilizes the non-isotopic method of enzyme-linked assay for detection of HIV in the amplified product after PCR. HIV RNA extracted from plasma was amplified by RT-Nested-PCR using biotinylated-inner primers of gag, pol and env regions, respectively. The PCR product was visualized by 5% polyacrylamide gel electrophoresis and ethidium bromide staining. The heat-denatured PCR product was hybridized with HIVcDNA of each region which was immobilized to a microplate. The hybridized microplate was reacted with streptavidin-conjugate peroxidase and then the optical density(O.D.) was read at 490nm. The cut off value was determined at O.D. 0.25. The results of the electrophoresis of gag, pol and env regions were all positive in 53 HIV-1 seropositive samples from Japan and the USA, and all negative in 55 HIV-1 seronegative samples. Using the MH technique, USA samples showed a higher O.D. than the Japan samples, particularly in the pol region. The results of MH technique in gag and pol regions coincided with that of electrophoresis. But, one of 27 Japanese HIV-1 seropositive samples showed O.D. of less than 0.2 in only env region. This particular sample was classified by V3 peptide-based enzyme immunoassay as subtype E, which differs from the typical subtype B of Japan and USA samples. This suggests the presence of several genotypes in HIV-1 seropositive individuals in Japan. Based on this data, the MH technique using gag, pol and env region is a simple, sensitive, safe and specific assay for detection of HIV-1 RNA in plasma, and would be useful in clinical testing.
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PMID:[Detection of HIV-1 in plasma samples using microplate hybridization after RT-PCR]. 899 Sep 36

The transcriptional regulatory elements of many inducible T-cell genes contain adjacent or overlapping binding sites for the Ets and NF-kappaB/NFAT families of transcription factors. Similar arrays of functionally important NF-kappaB/NFAT and Ets binding sites are present in the transcriptional enhancers of human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2), suggesting that this pattern of nuclear protein binding sites reflects an evolutionarily conserved mechanism for regulating inducible T-cell gene expression that has been co-opted during HIV evolution. Despite these findings, the molecular mechanisms by which Ets and NF-kappaB/NFAT proteins cooperatively regulate inducible T-cell gene expression remained unknown. In the studies described in this report, we demonstrated a physical interaction between multiple Ets and NF-kappaB/NFAT proteins both in vitro and in activated normal human T cells. This interaction is mediated by the Ets domain of Ets proteins and the C-terminal region of the Rel homology domains of NF-kappaB/NFAT proteins. In addition, the Ets-NF-kappaB/NFAT interaction requires the presence of DNA binding sites for both proteins, as it is abolished by the DNA intercalating agents propidium iodide and ethidium bromide and enhanced by the presence of synthetic oligonucleotides containing binding sites for Ets and NF-kappaB proteins. A dominant-negative mutant of NF-kappaB p50 that binds DNA but fails to interact with Ets proteins inhibits the synergistic activation of the HIV-1 and HIV-2 enhancers by NF-kappaB (p50 + p65) and Ets-1, suggesting that physical interaction between Ets and NF-kappaB proteins is required for the transcriptional activity of the HIV-1 and HIV-2 enhancers. Taken together, these findings suggest that evolutionarily conserved physical interactions between Ets and NF-kappaB/NFAT proteins are important in regulating the inducible expression of T-cell genes and viruses. These interactions represent a potential target for the development of novel immunosuppressive and antiviral therapies.
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PMID:Physical interactions between Ets and NF-kappaB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells. 909 28

Tat (transactivator of transcription) is essential for HIV-1 replication in vivo and in vitro. Tat-(65-80), an RGD containing domain, has been shown to regulate proliferative function of a variety of cell lines, including a human adenocarcinoma cell line, A549. The exact cellular and molecular mechanisms by which these effects are mediated, remain unknown. To evaluate the hypothesis that Tat-(65-80) modulates the expression of immediate early genes (IEG) c-jun, c-myc, c-fos and the tumor suppressor gene p53, serum starved A549 cells were incubated with Tat-(65-80) or heat-inactivated Tat-(65-80) at 10 ng/ml. Total cellular RNA was isolated from the cells at various time points (0-24 hours). In each case, 5 micrograms of RNA was reverse transcribed in 20 microliters of reaction volume. Equal amounts of cDNA were subjected to polymerase chain reaction (PCR) and analyzed by electrophoresis. The photographic negatives of the ethidium bromide stained gels were quantitated by densitometric scanning and normalized to corresponding beta-actin PCR products. Treatment with Tat-(65-80) showed a twofold induction of c-jun at 0.5 h. Peak expression occurred at 60 minutes and remained above baseline at 24 hours (h). c-myc was increased at 0.5 h, reached a twofold increase at 2 h and remained above baseline at 24 h. c-fos increased seven fold at 0.5 h and declined subsequently to baseline at 8 h. p-53 gene was reduced fivefold at 0.5 h and remained downregulated thereafter. These results show that Tat-(65-80) can modulate growth related genes in human lung epithelial cells.
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PMID:An RGD containing peptide from HIV-1 Tat-(65-80) modulates protooncogene expression in human bronchoalveolar carcinoma cell line, A549. 912 88

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