Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that 9-nitrocamptothecin (9NC) inhibited human immunodeficiency type 1 (HIV-1) replication in latently HIV-1-infected T lymphocytic ACH-2 cells stimulated with the cytokine tumor necrosis factor alpha (TNF-alpha) (Moulton et al., AIDS Res Hum Retroviruses 1998;14:39). 9NC induced an accelerated apoptosis in HIV-1-infected, but not uninfected, lymphocytic cells. The present study demonstrates that 9NC selectively inhibits release of HIV-1 from freshly infected monocytoid U937 cells in a dose-response manner. Significant inhibition was achieved with concentrations of 9NC that were not toxic. In contrast, HIV-1 replication in 9NC-resistant monocytoid cells, derived from U937, was not inhibited by similar doses of 9NC. Importantly, sensitivity of HIV-1 replication to 9NC correlated with the effect of 9NC on topoisomerase I (topo I) activity. In a 9NC-sensitive subline, 9NC induced posttranslational activation of the nuclear transcription factor kappaB (NF-kappaB) after the drug treatment. This activation was neither related to selective 9NC suppression of HIV-1 replication, nor was it sufficient for the 9NC-induced toxicity in the drug-sensitive monocytoid cells. Taken together, the selective inhibition of HIV-1 replication in both lymphoid and monocytoid cells lends further credence to the potential development of 9NC as an alternative drug for treating HIV-1 infection.
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PMID:9-nitrocamptothecin selectively inhibits human immunodeficiency virus type 1 replication in freshly infected parental but not 9-nitrocamptothecin-resistant U937 monocytoid cells. 1005 54

The plant alkaloid camptothecin (CPT) has demonstrated the ability to inhibit replication of the equine anemia virus (E1AV) and the human immunodeficiency virus (HIV) in infected cells in culture. Further, CPT prevented the development of lymphoma and erythroleukemia in mice infected with the Moloney murine leukemia virus and the Friend erythroleukemia virus, respectively, as assessed by prevention or reduction of splenomegaly. These results were observed at concentrations that had no apparent toxic effects on the mice. It has been suggested that the antiretroviral activity of CPT is mediated by the host cell's enzyme topoisomerase I. Taken collectively, the findings indicate that CPT analogues may develop into potent drugs against various human and animal diseases caused by diverse retroviruses. Copyright 1996 S. Karger AG, Basel
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PMID:Camptothecin: A Promising Antiretroviral Drug. 1172 78

Replication of human immunodeficiency virus type 1 (HIV-1) is regulated at reverse transcription. Cellular topoisomerase I has been reported to be carried into HIV-1 virions and enhance cDNA synthesis in vitro, suggesting that topoisomerase I expressed in virus producer cells regulates reverse transcription. Here, by employing both indicator cell assay and endogenous reverse transcription (ERT) assay, we show that topoisomerase I and adenosine triphosphate (ATP) enhanced cDNA synthesis of HIV-1. In addition, topoisomerase I mutants, R488A and K532A, lacking enzymatic activity, attenuated the efficiency of cDNA synthesis and resulted in inhibition of the infectivity of HIV-1, suggesting that the activity of topoisomerase I lacking in these mutants is indispensable for the cDNA synthesis in the HIV-1 replication process. Furthermore, ATP could dissociate topoisomerase I from the topoisomerase I-RNA complex and enhance cDNA synthesis in vitro. These findings suggest that cellular topoisomerase I and ATP play a pivotal role in the synthesis of cDNA of HIV-1.
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PMID:Topoisomerase I and ATP activate cDNA synthesis of human immunodeficiency virus type 1. 1205 40

Replication of Streptomyces linear chromosomes and plasmids proceeds bidirectionally from a central origin, leaving recessed 5' termini that are extended by a telomere binding complex. This complex contains both a telomere-protecting terminal protein (Tpg) and a telomere-associated protein that interacts with Tpg and the DNA ends of linear Streptomyces replicons. By using histidine-tagged telomere-associated protein (Tap) as a scaffold, we identified DNA polymerase (PolA) and topoisomerase I (TopA) proteins as other components of the Streptomyces telomere complex. Biochemical characterization of these proteins indicated that both PolA and TopA exhibit highly efficient reverse transcriptase (RT) activity in addition to their predicted functions. Although RT activity innate to other DNA-dependent DNA polymerases has been observed previously, its occurrence in a topoisomerase is unprecedented. Deletion mapping and sequence analysis showed that the RT activity of Streptomcyces TopA resides in a peptide region containing motifs that are absent from most bacterial topoisomerases but are highly conserved in a novel subfamily of eubacterial topoisomerases found largely in Actinobacteria. Within one of these motifs, and essential to the RT function of Streptomyces TopA, is an Asp-Asp doublet sequence required also for the RT activities of human immunodeficiency virus and eukaryotic cell telomerases.
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PMID:Reverse transcriptase activity innate to DNA polymerase I and DNA topoisomerase I proteins of Streptomyces telomere complex. 1545 10

Talaroflavone (1) and 1-deoxyrubralactone (2) are natural compounds isolated from cultures of a fungal strain derived from sea algae, and their structures were determined by spectroscopic analyses. Compound 2 is a novel rubralactone derivative, 6-hydroxy-8-methoxy-1-methyl-1,2,3a,9b-tetrahydrocyclopenta[c]isochromene-3,5-dione. These compounds selectively inhibited the activities of families X and Y of eukaryotic DNA polymerases (pols), and compound 2 was a stronger inhibitor than compound 1. The IC(50) values of compound 2 on rat pol beta, which is a pol of family X, and human pol kappa, which is a pol of family Y, were 11.9 and 59.8 microM, respectively. On the other hand, compounds 1 and 2 did not influence the activities of the other families of eukaryotic pols, such as family A (i.e., pol gamma) and family B (i.e., pols alpha, delta, and epsilon), and showed no effect even on the activities of plant pols alpha and beta, prokaryotic pols, and other DNA metabolic enzymes, such as calf primase of pol alpha, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerase I and II, T4 polynucleotide kinase, and bovine deoxyribonuclease I. This is the first report about the selective inhibitors of families X and Y of eukaryotic pols.
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PMID:1-deoxyrubralactone, a novel specific inhibitor of families X and Y of eukaryotic DNA polymerases from a fungal strain derived from sea algae. 1817 92


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