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

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

Several previously unnoticed genes in the human immunodeficiency virus type 1 (HIV-1), potentially encoding selenoproteins, have been discovered by analyzing the genomic RNA structure and its relation to novel open reading frames. We have found a number of new potential RNA pseudoknots, including one in the long terminal repeat, several that coincide with highly conserved enzyme active site sequences in the pol coding region, and one in the env coding region. These pseudoknots can potentially direct the synthesis of selenocysteine (SeC) containing--1 frameshift fusion proteins. This is possible because we have found potential SeC insertion sequences (SECIS) in the RNA of HIV and other retroviruses; such structures are known to be necessary and sufficient for the incorporation of SeC at UGA "stop" codons anywhere in a eukaryotic mRNA. In several locations, UGA codons in the -1 reading frame are highly conserved across a broad spectrum of primate immunodeficiency viruses. Due to the degeneracy of the genetic code, this conservation cannot be explained by evolutionary selection of the pol gene protein sequence alone. Such observations, combined with the conservation of the associated reading frames, strongly suggest that these are real genes, and thus that the pseudoknots are also real. A protease pseudoknot-directed -1 frameshift fusion protein contains a highly conserved SeC codon and has significant similarities to a number of DNA binding proteins, including papillomavirus E2 proteins, suggesting it may be a virally encoded repressor of HIV transcription when cleaved by protease from the rest of the gag-pol gene product. A reverse transcriptase (RT) frameshift fusion protein replaces the RT active site with a highly conserved SeC-containing module. An integrase frameshift fusion protein contains the N-terminal integrase DNA-binding domain and a potential ATP-binding "GKS" motif; it has significant similarities to several helicases, but no SeC codons. A potential frameshift fusion protein from env has one SeC codon, but not in a highly conserved position. SeC incorporation could extend the nef gene product by 33 residues through the C-terminal UGA codon without frameshifting, potentially leading to substantial SeC utilization in infected cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A basis for new approaches to the chemotherapy of AIDS: novel genes in HIV-1 potentially encode selenoproteins expressed by ribosomal frameshifting and termination suppression. 806 94

Topoisomerase I activity was detected in detergent-disrupted human immunodeficiency virus type 1 (HIV-1) particles. The enzyme did not require ATP for its conversion of SC DNA to an RC form, had divalent cation requirements similar to those of eukaryotic topoisomerase I, and was significantly inhibited by the specific topoisomerase I inhibitor camptothecin. However, camptothecin failed to inhibit replication of HIV in infected cells at nontoxic concentrations, and an active site motif for topoisomerase I could not be detected on the HIV genome. These results suggests that HIV does not encode a novel topoisomerase I, but rather packages the cellular enzyme.
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PMID:Cellular topoisomerase I activity associated with HIV-1. 814 41

Evidence supports the premise that a pro-oxidant condition exists in HIV-seropositive patients, a result of an overabundance in production of reactive oxygen forms combined with a multilevel deficiency in nutritional and metabolic sources of antioxidants. Apoptosis (a programmed cell death) is recognized as a possible pathway of immune cell loss in patients with HIV infection and AIDS. The cascade of events that results from 'oxidative stress' (OS) is markedly similar to that which can initiate apoptosis and includes oxidation of cellular membranes, alteration of metabolic pathways, disruption of electron transport systems, depletion of cellular ATP production, loss of Ca2+ homeostasis, endonuclease activation and DNA/chromatin fragmentation. Downstream events secondary to these effects may also play a role in activation of latent virus and subsequent viral replication. Primary and secondary metabolites found in plants act as synergistic antioxidants, and can protect plants from oxidation-induced cell death. Experiments have shown that some of these same metabolites can inhibit cell killing by HIV. Can these compounds be useful in inhibiting viral activation and the death of immune cells in HIV/AIDS through their synergistic antioxidant properties? A brief review of the evidence for OS in HIV is presented and the potential basis for OS playing a role in the initiation of cell death and viral replication is explored. The functional antioxidant activities of plant metabolites are illustrated and the use of these synergistic antioxidants from plants are proposed as a mechanism by which viral replication and cell killing in HIV infection can be inhibited.
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PMID:Could oxidative stress initiate programmed cell death in HIV infection? A role for plant derived metabolites having synergistic antioxidant activity. 819 35

In situ hybridization of human immunodeficiency virus-1 (HIV-1) has been performed on eight eyes from eight distinct acquired immune deficiency syndrome patients (three cases had a normal fundus examination and five presented with cytomegalovirus retinitis). The eyes were removed at autopsy and frozen immediately. Contiguous 10-mu cryostat sections were obtained and tested with a HIV probe labeled by nick-translation with [35S]-ATP. HIV-1 RNA was detected in the retina of two acquired immune deficiency syndrome patients. The first positive case presented with typical ophthalmological and histopathological cytomegalovirus retinitis, the second one was not related to cytomegalovirus, according to clinical or histopathological classical criterias. HIV-1 was localized in retinal vascular walls. This shows that there is an active replication of HIV in retina of some acquired immune deficiency syndrome patients.
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PMID:In situ hybridization of HIV-1 RNA in retinal vascular wall. 823 45

Human immunodeficiency virus type 1 (HIV-1) encodes a regulatory protein, Rev, which is required for cytoplasmic expression of incompletely spliced viral mRNA. Rev binds to a cis-acting Rev-responsive element (RRE) located within the env region of HIV-1. It has previously been shown that a 17-amino-acid peptide, corresponding to the basic domain of Rev, specifically inhibited in vitro the splicing of mRNAs containing the RRE. In this reaction, the peptide acts after an ATP-dependent step in the spliceosome assembly resulting in an accumulation of a 45-50S splicing-deficient complex. Characterization of this complex revealed that the basic domain of Rev does not interfere with U1 small nuclear ribonucleoprotein binding but blocks the entry of U4, U5, and U6 small nuclear RNAs into the spliceosome. Binding of U2 small nuclear ribonucleoprotein was partially inhibited. The critical nature of the oligomeric structure of RRE has been investigated both in vitro and in vivo. Reporter genes that contained one, three, or six repeated-monomer high-affinity Rev binding sites (IIB) within an intron yielded a correlation among the oligomeric state of bound Rev; inhibition of splicing; ability to block the assembly of U4, U5, and U6 small nuclear RNAs in the spliceosome in vitro; and level of Rev response in vivo.
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PMID:The basic domain of Rev from human immunodeficiency virus type 1 specifically blocks the entry of U4/U6.U5 small nuclear ribonucleoprotein in spliceosome assembly. 833 28

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

Despite its recognition as the most prevalent HIV associated cancer, speculation still abounds regarding the pathogenesis of AIDS-related Kaposi's sarcoma (AIDS-KS). However, it has been established that both cytokines, e.g. IL-6, and HIV-associated products, e.g., Tat, are integral in AIDS-KS cellular proliferation. Further, both experimental and clinical evidence is accumulating to link reactive oxygen intermediates (ROI) with both cytokine induction (primarily via nuclear factor-kappa B[NF-kappa B] dependent routes) as well as the subsequent cytokine, tumor necrosis factor alpha (TNF alpha) stimulation of HIV replication. Features of AIDS-KS patients, such as retention of phagocytes, presence of sustained immunostimulation, and a frequent history of KS lesions arising at traumatized sites, make oxidant stress a viable clinical factor in AIDS-KS development. Time course nucleotide profile analyses show that AIDS-KS cells have an inherent, statistically significant, biochemical deficit, even prior to oxidant stress, due to 1) a more glycolytic bioenergetic profile, resulting in lower levels of high energy phosphates (impairing capacity for glutathione [GSH] synthesis and DNA repair); 2) lower levels of NADPH (compromising the activities of GSSG reductase and peroxidase function of catalase); and 3) reduced levels of GSH (impeding both GSH peroxidase and GSH-S-transferases). Following exposure to physiologically relevant levels of H2O2, only the human microvascular endothelial cells (a putative AIDS-KS progenitor cell) responded with bioenergetic adaptations that reflected co-ordination of energy generating and cytoprotective pathways, e.g., retention of the cellular energy charge, increased NAD+, and an accentuation of the ATP, NADPH, and total adenine nucleotide differences relative to AIDS-KS cells. Also, some of the AIDS-KS strains retained intracellular GSSG subsequent to oxidant challenge, inviting the formation of deleterious protein mixed disulfides. While the results of our study address some AIDS-KS issues, they also raise an etiological question, i.e., Does the inability to tolerate oxidant stress arise in conjunction with AIDS-KS neoplastic development, or is it pre-existing in the population at risk? Regardless, use of antioxidant therapy (low risk/ potentially high benefit) in both the "at risk" population as well as in those individuals with active disease may prove a useful preventative and/or treatment modality.
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PMID:Cultured AIDS-related Kaposi's sarcoma (AIDS-KS) cells demonstrate impaired bioenergetic adaptation to oxidant challenge: implication for oxidant stress in AIDS-KS pathogenesis. 856 50

Recombinant Nef-protein of HIV-1 Bru derived from Escherichia coli revealed heparin-binding activity. This property was used to purify the Nef-protein by a one-step procedure, yielding about 90% homogenous Nef-protein as evaluated by silver staining. The Nef-protein was soluble without denaturing agents. Native folding of Nef was demonstrated with antibodies against conformational epitopes of Nef by a slot blot assay under native conditions. Despite its affinity to heparin and its nuclear localization in persistently HIV-1 infected glioblastoma cells (Kohleisen et al., 1992), Nef did not show DNA-binding properties by slot blot/hybridization assay and South/Western blot. In nucleotide-binding assays a strong autophosphorylation activity with [gamma-32P]ATP was observed. Nef-protein was not a substrate for ADP-ribosylation by bacterial toxins arguing against G-protein-like activities of Nef. Recombinant Nef did not interact with membranes as shown by the lack of increased fluorescence emission of Nef in the presence of liposomes. The recombinant Nef-protein obtained by one-step heparin-based purification shares immunological properties with native Nef and should prove useful for further studies of Nef function and immunogenicity.
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PMID:Heparin-binding capacity of the HIV-1 NEF-protein allows one-step purification and biochemical characterization. 879 10

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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