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

Some sugar modified analogs of 2'-deoxy-E-5-styryluridine triphosphates were synthesized and examined for their inhibitory effects on eukaryotic DNA polymerases and HIV-1 reverse transcriptase. Among these compounds, 3'-azido-2',3'-dideoxy-E-5-styrylUTP (6) and 2',3'-dideoxy-E-5-styrylUTP (7) showed remarkable inhibitory effects on reverse transcriptase. The mode of action and the influence of the substituent at C-5 of 2',3'-dideoxyUTP analogs will be described.
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PMID:Inhibitory effects of 2'-deoxy-5-styryluridine 5'-triphosphate analogs on retroviral reverse transcriptase and eukaryotic DNA polymerases. 128 6

Previously, we have reported that conjugation of antisense oligonucleotides to poly(L-lysine) (PLL) lowers their inhibitory concentration in several biological models. We have now tested these conjugates for inhibition of human immunodeficiency virus type 1 (HIV-1) replication. PLL-conjugated oligonucleotides complementary to the translation initiation site of Tat protein protect cells from the cytopathic effect of HIV-1 in acute infection assays. The EC50 of conjugates is approximately 0.15 microM, which represents a strong reduction in concentration as compared to nonconjugated oligonucleotides (EC50 = 20 microM). In contrast with most reports in the literature, we have observed sequence specific antiviral effects with PLL conjugates. This was particularly noteworthy in antiviral experiments performed with HIV-1 isolates presenting heterogeneity in the 5' end of the tat mRNA sequence. Two mismatches at the target site were sufficient to reduce very significantly the antiviral activity of the conjugates but did not modify the effect of nonconjugated oligonucleotides. Unlike free oligonucleotides, PLL-conjugated ones do not interfere with virus penetration and/or reverse transcription as demonstrated by polymerase chain reaction (PCR) analysis of viral DNA.
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PMID:Poly(L-lysine)-conjugated oligonucleotides promote sequence-specific inhibition of acute HIV-1 infection. 128 42

DNA fragments coding for a variety of different viral antigens have been cloned and expressed in Escherichia coli. Selected purified recombinant antigens were used for detection of specific antibodies by means of the ELISA technique. This approach has been used for the development of four different ELISAs for the detection of HIV- and EBV-specific antibodies.
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PMID:Recombinant antigens in viral diagnosis. 128 74

Mechanisms of the effects of the dTTP analogues 3'-azido-3'-deoxythymidine 5'-triphosphate (AZTTP) and 3'-amino-3'-deoxythymidine 5'-triphosphate (NH2 TTP) upon the HIV-1 reverse transcriptase (RT) are discussed. These compounds block the RT in vitro and do so by different kinetic mechanisms. Infidelity of replication is a hallmark of the HIV-1 RT, and replication errors by the enzyme on RNA and DNA templates are discussed. The enzyme's infidelity has ramifications for inhibition: On the one hand, the propensity to produce mutations enhances the ability of the virus to escape inhibitors whereas on the other hand, the infidelity of the reverse transcriptase may allow the development of imaginative inhibitor strategies.
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PMID:Inhibitors of HIV-1 reverse transcriptase and fidelity of in vitro DNA replication. 128 1

Ten patients with chronic type B hepatitis were treated for four weeks with a rapidly tapered dose of oral prednisone (initial dose, 40 mg/d) followed by two weeks of no therapy followed by four weeks of oral acyclovir (600 mg/d). Liver biochemistry, HBsAg, HBeAg, DNA-polymerase and HBV-DNA levels in serum were determined prior to, during and for six months following therapy. The mean age +/- SD of the study population was 33 +/- 15 years (range 18-58). Nine of the patients were male. Four patients were Caucasian and six of Southeast Asian origin. Three patients were homosexual, all HIV antibody negative. The mean ALT level prior to treatment was 89 +/- 62 IU/L (range: 30-214). During the six month post-treatment follow-up period, 5/8 (63%) patients became DNA-P negative and 6/10 (60%) HBV-DNA negative. One responder reverted to DNA-P positive (final response, 50%) and another to HBV-DNA positive (final response, 50%) prior to completion of the study. Patients were more likely to become DNA-P or HBV-DNA negative if they had elevated pre-treatment ALT values and low levels of DNA-P and HBV-DNA. HBeAg became undetectable in 3/10 (30%) individuals, one of whom reverted to positive at the end of the follow-up period (final response, 20%). All patients remained HBsAg positive. Mild fatigue, which occurred in four individuals, was the most common side effect. The results of this study suggest that a controlled clinical trial of oral prednisone/acyclovir is warranted in the treatment of adults with chronic type B hepatitis.
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PMID:A pilot study of steroid withdrawal followed by oral acyclovir in the treatment of chronic type B hepatitis. 128 32

A highly sensitive two-step polymerase chain reaction (PCR) method was evaluated for detection of human immunodeficiency virus type 1 (HIV-1) DNA in clinical specimens. The product resulting from the first amplification reaction is used as the template for the second PCR with an internal (nested) primer pair. Even when starting from a single copy of HIV-1 DNA, the double PCR product was readily detected by direct visualization in ethidium bromide-stained agarose gels. Amplification of minute amounts of HIV-1 DNA was successful in a considerable excess of HIV-1 negative DNA than reported previously. All of 85 HIV-1-infected individuals were PCR-positive with at least two of the three sets of primers used, 252 of 255 amplifications allowing unambiguous visualization of a unique DNA fragment of the expected size. The two-step amplification protocol is simple and rapid and fulfills the requirements of sensitivity and specificity for use in a clinical laboratory.
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PMID:Nested polymerase chain reaction for detection of human immunodeficiency virus type 1 DNA in clinical specimens. 128 30

We used polymerase chain reaction (PCR) to amplify a segment, about 560 base pairs (bp), of HIV-1 gag DNA prepared from peripheral blood mononuclear cells of a seropositive Taiwanese pair of mother and infant. TM-1 and TC-1 clones of PCR-amplified DNA derived from the mother and infant, respectively, showed a 94.5% homology with each other. However, the TM-1 and TC-1 sequences exhibited lower degrees of homology, i.e. only 85.1% and 85.8%, respectively, with the corresponding gag segment of a North American HIV-1 subtype (HXB2), and 86.4% and 87.0%, respectively, with that of a Zairean HIV-1 subtype (Z2Z6). The divergence of TM-1 and TC-1 sequences from those of HXB2 and Z2Z6 is particularly prominent in the first (5' proximal) 200 bp of the cloned DNA segment, involving transitions more frequently than transversions. Two additional clones TM-2 and TC-2 derived from the mother and infant were sequenced for the first 200 bp. These four clones showed a high degree of homology (94.7-97.5%) among themselves, providing an evidence for transmission of the virus from the mother to the infant. These findings show the epidemiological value of PCR, and indicate the presence of a gag subtype of HIV-1 which is distinct from both the North American and Zairean subtypes according to the phylogenetic tree constructed.
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PMID:A vertically transmitted HIV-1 gag-subtype variant detected in Taiwan. 129 63

The anti-HIV activities of two new polyanionic polymers (AM 242 and AM 612) were investigated in cell culture-based and biochemical antiviral assays. These compounds inhibited the reverse transcriptases from HIV-1 and HIV-2, using enzyme purified from virions and either a ribosomal RNA or gapped duplex DNA as the template. With the ribosomal RNA template, AM 242 and AM 612 had ID50 values of 1.1 and 0.10 micrograms/ml against the HIV-1 reverse transcriptase. In vitro cell based assays determined that both compounds significantly inhibited both the cytopathic effects associated with HIV-1 infection and the replication of virus in infected cells. AM 242 had an IC50 of approximately 1.0 micrograms/ml, while that of AM 612 was 0.19 micrograms/ml. These two active polyanionic polymers were effective in inhibiting the growth of a panel of HIV-1 isolates and were also active against HIV-2. Although the compounds were toxic at high concentration, they had antiviral activity over a wide range of nontoxic concentrations, yielding a high selectivity index. AM 612 was 100% protective for CEM cells from 320 ng/ml to 1 microgram/ml. Both compounds caused a significant increase in cellular proliferation as determined by the concentration-dependent increase in incorporation of radioactive precursors into cellular macromolecules.
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PMID:Significant anti-HIV activity of new modified polyanionic polymers in vitro. 129 18

HIV infection leads to the production of virus-specific antibodies which are usually detectable by 12 weeks following exposure. Development of the antibody response, however, depends upon many factors and may require longer periods of time. The authors report findings from the monitoring of 33 female prostitutes from Djibouti, East Africa, at risk for acquiring sexually transmitted infections over a 5-month period for evidence of seroprogression and/or seroconversion for HIV-1, HIV-2, and HTLV-I. All sera were initially reactive by at least one retroviral screening assay, but most produced negative or indeterminate results by Western blot assays. Five months after the initial screening, Western blot assays indicated that one individual exhibited full seroconversion for HIV-1, one HIV-1 positive individual also became positive for HIV-2, and two subjects showed seroprogression to become HTLV-I confirmed positive. Sera from 14 individuals produced indeterminate results by Western blot for HIV-1, ten of which were previously negative. The remaining four exhibited reactivity to at least one additional viral specific antigen after the five months. Circulating HIV-1 antigen was not demonstrated in any of the sera, but DNA isolated from one of the individuals with indeterminate results produced a positive reaction for HIV-1 by polymerase chain reaction.
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PMID:Monitoring for HIV-1, HIV-2, HTLV-I sero-progression and sero-conversion in a population at risk in east Africa. 129 80

The main goal of the present paper was to analyze the molecular diversity of the principal neutralizing domain (V3 loop) of the HIV 1 gp120 in samples from patients of Argentina. The study was carried out on a total of 30 HIV 1 positive blood samples, obtained during 1991-1992, belonging to 15 intravenous drug users (group A), 5 homosexual men (group B), 8 children born to HIV 1 positive mothers (group C) and 2 AIDS patients (group D). By using extracted DNA from peripheral blood lymphocytes and from infected cells of the viral isolates in the case of the 2 AIDS patients, the V3 loop region was amplified by means of polymerase chain reaction. Direct sequencing by Sanger methodology was then performed on DNA fragments and nucleotide sequences obtained were translated into the correspondent amino acids. Consensus sequences for each group and a general consensus sequence were established (Table 1). Its alignment with V3 loop amino acid sequences of the major HIV 1 strains isolated worldwide is showed in table 2. Homology analysis between each sequence of the study population and sequence of different HIV 1 isolates showed that most of these samples share high homology with SF2 and BH10 strains. In contrast a low homology was found with JH3 and MN isolated (table 3). The presence of highly conserved amino acid residues as substitutions and insertions was determined in the Argentinian V3 loop sequences giving them a local pattern. The present paper is of great importance for our country, considering that the V3 loop is the main neutralizing domain becoming a major target in the development of HIV 1 vaccine. To our knowledge, this is the first report on the sequencing of the principal neutralizing domain of the Human Immunodeficiency Virus type 1 in Latin America.
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PMID:[Molecular analysis of the principal neutralization epitope (V3 loop) of human immunodeficiency virus type 1 in Argentina]. 129 19


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