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

Early events in the retroviral replication cycle include the conversion of viral genomic RNA into linear double-stranded DNA. This process is mediated by the reverse transcriptase (RT), a multifunctional enzyme that possesses RNA-dependent DNA polymerase, DNA-dependent DNA polymerase, and RNase H activities. In the course of studies of a recombinant RT of human immunodeficiency virus type 1 (HIV-1), we observed an additional, unexpected activity of the enzyme. The purified RT catalyzes a specific cleavage in HIV-1 RNA hybridized to tRNALys, the primer for HIV-1 reverse transcription. The cleavage at the primer binding site (PBS) of HIV RNA is dependent on the double-stranded structure of the HIV RNA-tRNALys complex. This RNase activity appears to be distinct from the RNase H activity of HIV-1 RT, as the substrate specificity and the products of the two activities are different. Moreover, Escherichia coli RNase H and avian myeloblastosis virus RT are unable to cleave the HIV RNA-tRNALys complex. We refer to this unusual activity as RNase D. Two lines of evidence indicate that the specific RNase D activity is an integral part of recombinant HIV RT. The specific RNase D activity comigrates with the other RT activities, DNA polymerase, and RNase H upon filtration on a Superose 6 gel column or chromatography on a phosphocellulose column. Moreover, three recombinant HIV-1 RT preparations expressed and purified in different laboratories by various procedures exhibit RNase D activity. Sequence analysis indicated that RNase D activity cleaves the substrate HIV-1 RNA-tRNALys at two distinct sites within the PBS sequence 5'-UGGCGCCCGA decreases ACAG decreases GGAC-3'. The sequence specificity of RNase D activity suggests that it might be involved in two stages during the reverse transcription process: displacement of the PBS to enable copying of tRNALys sequences into plus-strand DNA or to facilitate the second template switch, which was postulated to occur at the PBS sequence.
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PMID:Double-stranded RNA-dependent RNase activity associated with human immunodeficiency virus type 1 reverse transcriptase. 137 Oct 14

Crude extracts of four Chinese herbs, Arctium lappa, Astragalus membranaceus, Andrographis paniculata, and Prunella vulgaris, were assessed in several tissue culture lines for anti-HIV activity and for cytotoxicity. One extract, obtained from P. vulgaris, was able to significantly inhibit HIV-1 replication with relatively low cytotoxicity. The active factor was purified using sequential precipitations with ethanol and n-butanol, followed by reverse-phase and gel permeation high-performance liquid chromatographic separations. The active component was anionic with a molecular weight of approximately 10 kDa. The purified extract inhibited HIV-1 replication in the lymphoid cell line MT-4, in the monocytoid cell line U937, and in peripheral blood mononuclear cells at effective concentrations of 6, 30, and 12.5 micrograms/ml, respectively. Pretreatment of uninfected cells with the extract prior to viral exposure did not prevent HIV-1 infection. By contrast, preincubation of HIV-1 with the purified extract dramatically decreased infectiousness. The purified extract was also able to block cell-to-cell transmission of HIV-1, prevented syncytium formation, and interfered with the ability of both HIV-1 and purified gp120 to bind to CD4. PCR analysis confirmed the absence of HIV-1 proviral DNA in cells exposed to virus in the presence of the extract. These results suggest that the purified extract antagonizes HIV-1 infection of susceptible cells by preventing viral attachment to the CD4 receptor.
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PMID:Mechanism of inhibition of HIV-1 infection in vitro by purified extract of Prunella vulgaris. 137 Oct 29

We have analyzed the limiting factors involved in the induction of human immunodeficiency virus type 1 (HIV-1) provirus expression by tumor necrosis factor-alpha (TNF-alpha), phorbol-12-myristate-13-acetate (PMA), and bryostatin-1 in T-cells (ACH-2) and monocytes (U1). We have demonstrated that, while there is a correlation among the increase of 9.2-kilodalton (kDa) HIV-1 RNA, the increase of viral proteins (p24) in the cells, and the release of HIV-1 virions into the medium, there is no direct correlation between the levels of induced NF-kappa B binding proteins and the expression of HIV-1 provirus. The presence of nuclear NF-kappa B-specific proteins appears to be essential only for the initiation of viral replication, since the HIV-1 transcripts could be detected in TNF-alpha or bryostatin-1-stimulated cells also at later times postinduction, times when no NF-kappa B proteins could be detected in the nucleus. The uv crosslinking of DNA and proteins has shown that TNF-alpha, PMA, and bryostatin-1 induce different sets of NF-kappa B binding proteins with distinct kinetics of binding.
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PMID:Activation of human immunodeficiency virus type 1 provirus in T-cells and macrophages is associated with induction of inducer-specific NF-kappa B binding proteins. 137 Oct 30

Using a quantitative polymerase chain reaction (PCR) method, we have previously shown that a molecularly cloned isolate of human immunodeficiency virus type 1 (HIV-1) can efficiently enter quiescent primary lymphocytes; however, the reverse transcription process is not completed in these cells. In this study, we further characterized the reverse transcription of HIV-1 in quiescent cells, and our results indicate that while initiation of reverse transcription occurs simultaneously in both activated and quiescent lymphocytes, it not only ends prematurely but also proceeds more slowly in quiescent cells. We also performed experiments to address the role of partial reverse transcripts as intermediates in the viral life cycle. We used azidothymidine either before or after infection with HIV-1 to prevent formation of and further DNA synthesis by partial reverse transcripts, respectively. Decreases in virus production from these cells following mitogenic stimulation indicated that partial reverse transcripts can contribute significantly to virus rescue from infected quiescent cells stimulated subsequent to infection. Furthermore, we established that mitogenic stimulation of infected quiescent cells induces reinitiation of DNA synthesis from partial reverse transcripts. However, the virus rescue is inefficient relative to the initial multiplicity of infection, and this is explained by inefficient completion of DNA synthesis from the partial reverse transcript. Thus, the arrest of reverse transcription in quiescent cells may play an important role in HIV-1 pathogenesis by contributing to the inefficient infection of potential target cells in the peripheral blood of HIV-1-infected individuals.
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PMID:Incompletely reverse-transcribed human immunodeficiency virus type 1 genomes in quiescent cells can function as intermediates in the retroviral life cycle. 137 Nov 73

Carbocyclic 2',3'-didehydro-2',3'-dideoxyguanosine (carbovir, NSC 614846) is an anti-retroviral agent that may be useful in the treatment of AIDS. We have examined the ability of (-)-enantiomeric carbovir triphosphate to inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (EC 2.7.7.49). A comparison of inhibition kinetics was made with 3'-azido-2',3'-dideoxythymidine triphosphate and phosphonoformate. Inhibition of the reverse transcriptase was evaluated using poly(rA).oligo(dT)12-18, poly(rC).oligo(dG)12-18, or influenza virion RNA template with a specific oligodeoxynucleotide as primer. (-)-Carbovir 5'-triphosphate was shown to be a potent inhibitor of HIV-1 reverse transcriptase with an apparent Ki similar to that of 3'-azido-2',3'-dideoxythymidine triphosphate. Chain elongation studies utilizing an MS2 RNA template showed that (-)-carbovir 5'-triphosphate terminated transcription at positions identical to those where dideoxy-GTP terminated. This indicates that (-)-carbovir 5'-monophosphate is incorporated into the newly synthesized DNA and terminates transcription at that point. We conclude that (-)-carbovir 5'-triphosphate is a potent inhibitor of the HIV-1 reverse transcriptase enzyme and that (-)-carbovir most likely inhibits HIV by activity at the triphosphate level by a combination of direct competition for binding of the natural deoxynucleoside triphosphates to the reverse transcriptase and chain termination.
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PMID:DNA chain termination activity and inhibition of human immunodeficiency virus reverse transcriptase by carbocyclic 2',3'-didehydro-2',3'-dideoxyguanosine triphosphate. 137 Dec 85

Interferon (IFN) plays an important role in the treatment and pathogenesis of HIV disease. Recent studies show beneficial effects of IFN alpha in the treatment of HIV-associated Kaposi's Sarcoma and early HIV-infection. Moreover, cell culture studies support these beneficial effects. HIV infection of monocytes is blocked by IFN alpha administered at the time of viral challenge. The IFN alpha-treated cells show no evidence of HIV infection. Viral gene products produced in monocytes infected with HIV then treated with IFN alpha gradually decrease to baseline. Large quantities of proviral DNA are seen in the HIV-infected IFN alpha-treated cells with little evidence for viral transcription suggesting true microbiological latency. While most viral infections of cells result in IFN production, HIV is a notable exception. Indeed, HIV does not induce monocytes to produce IFN alpha and blocks its production following poly(I).poly(c) stimulation. This allows HIV yet another mechanism to evade an important host antiviral response. Paradoxically, the appearance of IFN activity in sera of HIV-infected patients is associated with disease progression, not resolution. Recent observations showing that the interaction between HIV-infected monocytes and PBMC results in the production of IFN alpha s with reduced anti-HIV activity may help explain this paradox. Thus, IFN alpha plays an important but complex role in HIV disease. The elucidation of cellular factors that regulate the antiretroviral effects of IFN alpha may lead to the development of novel therapeutic strategies for HIV infection.
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PMID:Interferons in the persistence, pathogenesis, and treatment of HIV infection. 137 92

The in vitro fidelity of reverse transcriptase from human immunodeficiency virus type I (HIV-1 RT) upon copying an RNA template was measured using the phi Xam 16 reversion assay. A phi X174 sequence harboring the amber 16 codon was cloned into a transcription vector. RNA obtained from transcription by bacteriophage T7 RNA polymerase was used as a template for RNA-directed DNA synthesis by HIV-1 RT. An imbalance of dNTP concentrations during the reverse transcription step served to distinguish between errors that arose from the transcription step and errors from reverse transcription. The frequency of dGTP.U mismatches was determined to be 1/360, while dGTP.rA mismatches formed at a rate of 1/4600. These are 20-fold and sevenfold higher, respectively, than the error rates determined for the same sequence with a DNA template. Due to a high background of errors in the RNA template originating from the transcription step only upper limits for the frequency of three other mismatches can be given. The data indicate that the reverse transcription step of the HIV-1 replication cycle contributes significantly to the generation of mutant viruses.
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PMID:Fidelity of human immunodeficiency virus type I reverse transcriptase in copying natural RNA. 137 12

3'-Fluoro-2',3'-dideoxythymidine 5'-(alpha-methylphosphonyl)-beta,gamma- diphosphate and 2'-deoxythymidine-5'-(alpha-methylphosphonyl)-beta, gamma- diphosphate have been synthesized. Both compounds are incorporated into DNA chains during catalysis by reverse transcriptases of human immunodeficiency (HIV) and avian myeloblastosis (AMV) viruses, DNA polymerase beta from rat liver, terminal deoxynucleotidyl transferase from calf thymus and (at a very low rate) is by E. coli DNA polymerase I, Klenow fragment. The first compound is a termination substrate while the second is capable of multiple incorporation into the DNA chains. For instance, reverse transcriptase catalysis resulted in the appearance of 8 residues of second compound. DNA polymerases alpha and epsilon from human placenta incorporated none of the above compounds into DNA chains, although an inhibition of DNA synthesis by both compounds was observed with all enzymes mentioned. The 3'----5'-exonuclease activity of DNA polymerase I, Klenow fragment, hydrolyzed DNA fragments containing phosphonomethyl internucleoside groups, while such DNA fragments were resistant to the E. coli exonuclease III.
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PMID:Formation of phosphonester bonds catalyzed by DNA polymerase. 137 65

Adeno-associated virus (AAV) is a nonpathogenic parvovirus which normally requires helper adenovirus or herpes-virus for replication. We examined the growth of AAV type 2 in human lymphocytes and its possible interaction with HIV-1. Three B cell lines (CK-B, HS-2, and UC729) and four T cell lines (Molt-4, Jurkat, HUT78, and HUT78+HIV, which is persistently infected with HIV-1) were infected with AAV either in the presence or in the absence of adenovirus. AAV DNA was found in cells of all the lines following incubation with the virus, indicating absorption. AAV DNA replication occurred in most cell lines without particular preference for B or T cells, but only in the presence of helper virus, either adenovirus or Epstein-Barr virus. Expression of AAV proteins was examined by immunoblotting and ELISA, using sera specific for AAV Rep or capsid proteins. The level of AAV protein synthesis correlated with the efficiency of AAV DNA replication, and both varied between cell lines. The yield of infectious AAV was low in most cases, except in one T4 line (Jurkat), where AAV replication and protein synthesis in the presence of adenovirus were very extensive. In HUT78+HIV cells both adenovirus and AAV (in the presence of Ad2) replicated efficiently. The effects of adenovirus plus AAV coinfections on HIV-1 replication, measured by reverse-transcriptase (RT) activity, were mild. Infection with adenovirus or AAV alone resulted in a 60-70% increase in RT activity, while infection with AAV plus adenovirus resulted in a 20% decrease in RT activity. The yield of infectious AAV in this cell line was very low.
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PMID:Replication of adeno-associated virus type 2 in human lymphocytic cells and interaction with HIV-1. 137 38

Thirteen isolates of human immunodeficiency virus type 1 (HIV-1) obtained in coculture with peripheral blood lymphocytes were tested for in vitro susceptibility to zidovudine (ZDV). Seven isolates were obtained from patients who had never been treated with ZDV and six from patients receiving the drug. The seven isolates from untreated patients and four of six from treated patients were susceptible to ZDV. The two isolates from the patients treated for the longest periods were resistant to the drug. The presence of mutations at critical positions of the reverse transcriptase gene was investigated by direct sequencing of polymerase chain reaction (PCR)-amplified DNA and four isolates were found to be mutants. An isolate from an untreated patient showed a change at residue 70 of the reverse transcriptase and an isolate from a patient treated for 4 months showed a change at residue 67. A change at residue 215 was found only for the two drug-resistant isolates, which correlated with the results obtained by Larder et al. using isolates from MT-2 cell cocultures. These results suggest that any HIV isolate provided by conventional coculture could be confidently tested for ZDV susceptibility in order to study the emergence of resistance during long-term therapy.
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PMID:Susceptibility of HIV-1 isolates to zidovudine: correlation between widely applicable culture test and PCR analysis. 137 52

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