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

A model system was developed previously for disposal of solid laboratory waste that is both radioactive and heat sensitive, e.g., HIV. A double polypropylene bag with charcoal vent filter and absorbent was designed to meet requirements for both steam sterilization and disposal as solid radioactive waste. Earlier work demonstrated the effective containment of radioactive gases by the filter and inactivation of organisms as heat sensitive as HIV. We sought to broaden the application of this model to ensure inactivation of microorganisms that are more heat resistant than HIV. The efficacy of steam sterilization using water or solutions of iodophor, hypochlorite, or hydrogen peroxide was studied under constant temperature and time conditions. The systems were monitored with internal probes, physical, chemical, and biological indicators. Biological indicators documented inactivation when bags containing hydrogen peroxide (3%) were autoclaved for 60 min at 121 degrees C. Synergistic activity between hydrogen peroxide and autoclave conditions significantly reduced processing time.
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PMID:Autoclave inactivation of infectious radioactive laboratory waste contained within a charcoal filtration system. 206 Oct 40

An important aspect of the infection by the human immunodeficiency virus (HIV-1) type 1 is its clinical latency, suggesting that the virus itself or the provirus may remain latent for extended periods of time after primary infection. Certain heterologous viral proteins or chemical and physical agents are able to reactivate latent virus. Since a common denominator shared by these agents is the ability to cause stress response in cells, we have examined the effects of oxidative stress mediated by hydrogen peroxide (H2O2) on HIV-1 latently infected promonocytic cell line termed U1. After exposure to H2O2 in concentrations ranging from 0.1 to 2 mM, the viability of the U1 cells decreased during 24 h before recovery. At 24 h post stress, the U1 cells began to express virus as assessed by elevated reverse transcriptase activities in culture supernatants. Immunofluorescence carried out on stressed U1 cells using anti-HIV-1 polyclonal antibodies showed that H2O2 leads to HIV-1 gene expression activation, but not to a release of viral particles from damaged cells. Additionally, using a HeLa cell line containing integrated the bacterial chloramphenicol acetyl transferase (CAT) gene under the control of the HIV-1 long terminal repeat (LTR), we have shown that oxidative stress mediated by H2O2 allows transactivation of the viral LTR revealed by intracellular CAT activity. A stimulation factor of around 4 of CAT activity can be reached when these cells are treated with 0.5 mM H2O2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of human immunodeficiency virus type 1 by oxidative stress. 207 16

A new method is described for determining molecular structures from NMR data. The approach utilizes 2D NOESY back-calculations to generate simulated spectra for structures obtained from distance geometry (DG) computations. Comparison of experimental and back-calculated spectra, including analysis of cross-peak buildup and auto-peak decay with increasing mixing time, provides a quantitative measure of the consistence between the experimental data and generated structures and allows for use of tighter interproton distance constraints. For the first time, the "goodness" of the generated structures is evaluated on the basis of their consistence with the actual experimental data rather than on the basis of consistence with other generated structures. This method is applied to the structure determination of an 18-residue peptide with an amino acid sequence comprising the first zinc fingerlike domain from the gag protein p55 of HIV. This is the first structure determination to atomic resolution for a retroviral zinc fingerlike complex. The peptide [Zn(p55F1)] exhibits a novel folding pattern that includes type I and type II NH-S tight turns and is stabilized both by coordination of the three Cys and one His residues to zinc and by extensive internal hydrogen bonding. The backbone folding is significantly different from that of a "classical" DNA-binding zinc finger. Residues C(1)-F(2)-N(3)-C(4)-G(5)-K(6) fold in a manner virtually identical with the folding observed by X-ray crystallography for related residues in the iron domain of rubredoxin; superposition of all main-chain and Cys side-chain atoms of residues C(1)-K(6) of Zn(p55F1) onto residues C(6)-Y(11) and C(39)-V(44) of rubredoxin gives RMSDs of 0.46 and 0.35 A, respectively. The side chains of conservatively substituted Phe and Ile residues implicated in genomic RNA recognition form a hydrophobic patch on the peptide surface.
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PMID:High-resolution structure of an HIV zinc fingerlike domain via a new NMR-based distance geometry approach. 210 40

Chemical synthesis of large peptide fragments (from 18 to 66 amino acid residues long) of the gp110 envelope glycoprotein and of nef-protein from HIV-1 was achieved by the solid phase method. Stepwise assembling of the peptide chains was carried out automatically on 4-(oxymethyl)-phenylacetamidomethyl resin using the N-alpha-butyloxycarbonyl amino acids with benzyl-based side chain protecting groups. Two elongation protocols were used depending on the peptide chain length: a standard cycle, mainly characterized by a single coupling step (Boc-amino acid symmetrical anhydride in dimethylformamide), and an optimized one for large peptides, based on a double coupling strategy (Boc-amino acid symmetrical anhydride first in dimethylformamide, then in dichloromethane). Final cleavage of the peptide from the solid support was carried out by anhydrous hydrogen fluoride and crude peptides were purified by C18 reverse phase medium pressure liquid chromatography after molecular filtration. Characterization of the purified peptides was done by analytical HPLC, amino acid content determination, and circular dichroism analysis both in polar (H2O) and in non-polar (TFE) environments. Immunoreactivity of anti-nef positive sera from HIV-1 infected patients by ELISA with the synthetic peptides was investigated. The results showed four major antigenic regions of nef-protein and mainly the immunodominance of the N- and C-termini of the molecule. Several of these peptides should prove to be useful for both diagnosis and vaccination purposes.
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PMID:Large fragments of nef-protein and gp110 envelope glycoprotein from HIV-1. Synthesis, CD analysis and immunoreactivity. 218 58

Because of the possibility of transmitting communicable diseases, in particular the HIV virus, it has been recommended that all diagnostic contact lenses, including rigid lenses, be disinfected after each use. Hydrogen peroxide is a recommended disinfection agent, but its effect on rigid lens polymers is relatively unknown. We soaked 50 lenses of 5 different polymers in 3% hydrogen peroxide for 10 min and measured the base curves to determine if any changes occurred. Our results showed no statistically significant change in base curve for the lenses measured, but 22% of the lenses did exhibit a small amount of warpage (mean 0.0382 mm) of the base curve. We were not able to determine what caused these lenses, and not all the lenses, to warp. Under the conditions of this study, hydrogen peroxide does not appear to cause clinically significant parameter changes, but lenses should be checked for warpage before use.
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PMID:Rigid lens base curve stability upon hydrogen peroxide disinfection. 230 47

The crystal structure of 3'-azido-3'-deoxy-thymidine (AZT), an antiviral agent that inhibits HIV reverse transcriptase, has been determined from three-dimensional x-ray diffractometer data. The crystal structure contains two independent molecules of AZT forming a hydrogen bonded dimer but exhibiting different conformations. These conformations are different from those theoretically calculated by molecular mechanics methods. The azido groups associate with each other and interrupt the base stacking, forming a sandwich of two stacked bases. The close conformational similarity of AZT to thymidine explains why AZT is a good substrate for thymidine kinase. The selective inhibition of reverse transcriptase by AZT is not due to any conformational restrictions imposed by the azido group but likely due to their stereoelectronic properties.
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PMID:Conformation and sandwiching of bases by azido groups in the crystal structure of 3'-azido-3'-deoxy-thymidine (AZT), an antiviral agent that inhibits HIV reverse transcriptase. 245 15

Xylanpoly-(hydrogen sulphate) disodium salt with a molecular weight of about 6000 daltons (HOE/BAY 946) completely inhibited syncytium formation induced by the infection of T lymphocytes with HIV as well as viral replication at concentrations above 25 micrograms/ml. This dose was found to be inhibitory for several strains of HIV-1 and HIV-2. Low molecular weight fractions of the compound were less active against HIV, and high molecular derivatives were as active as HOE/BAY 946. A direct influence of the drug on the infectivity of the virus could not be demonstrated. The drug inhibited the reverse transcriptase of HIV. Treatment of permanently HIV-infected U937 cells resulted in a drastic reduction of virus particles released into the supernatant and points to an additional mode of action. A therapeutic effect of HOE/BAY 946 against retroviruses in vivo could be demonstrated in Friend leukaemia virus-infected mice. A clinical pilot study with the compound was started recently in Germany with AIDS patients who did not tolerate or refused to take zidovudine and with asymptomatic virus carriers.
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PMID:Inhibition of HIV and virus replication by polysulphated polyxylan: HOE/BAY 946, a new antiviral compound. 246 49

Natural antiviral activity can be mediated by the interferon-induced synthesis of 2',5'-oligoadenylates (2-5As) and subsequent RNase L activation by these molecules. Analogues of 2-5A that are biologically active and metabolically stable were synthesized and analyzed for antiviral activity against the human immunodeficiency virus type 1 (HIV-1). Replacement of the 3' hydroxyl group of the adenosine moieties of 2-5A with hydrogen atoms (i.e., cordycepin analogues of 2-5A) converted authentic 2-5A trimer into anti-HIV-1 agents in vitro. These cordycepin analogues of 2-5A also inhibited partially purified HIV-1 reverse transcriptase. Introduction of chirality into the 2',5'-phosphodiester internucleotide linkages or 5'-phosphate moieties of the 2-5A molecule (i.e., phosphorothioate analogues of 2-5A) converted authentic 2-5A into more potent inhibitors of HIV-1 reverse transcriptase. However, these phosphorothioate 2-5As demonstrated little or no anti-HIV-1 activity in vitro. Thus, some analogues of 2-5A may form a class of anti-HIV-1 drugs with possible pleiotropic activities that include activation of latent RNase L and inhibition of reverse transcription.
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PMID:Phosphorothioate and cordycepin analogues of 2',5'-oligoadenylate: inhibition of human immunodeficiency virus type 1 reverse transcriptase and infection in vitro. 247 14

Three-dimensional computer models for two segments of the C terminus of gp41, the transmembrane AIDS envelope protein, which may form amphipathic alpha-helices, have been generated using structure prediction techniques combined with energy minimization and molecular dynamics simulations. Regions gp41(772-790) and gp41(828-848) of the HXB2 strain of HIV-1 display extraordinarily high hydrophobic moment maxima as alpha-helices and when in an antiparallel conformation exhibit charge complementarity, implying that they may bind with each other and associate with the membrane. The feasibility of this hypothesis was tested in a series of computer simulations of these peptides, extended by several residues to include additional charge pairing. Beginning with a trial structure in the form of antiparallel alpha-helices of segments 770-794 and 824-856, systematic axial rotations and displacements were used to generate alternative initial states. Molecular dynamics simulations with alpha-helical torsional restraints yielded several approximately cylindrical dimeric structures highly stabilized by numerous salt links and other hydrogen bonds. This suggests that these two regions may fold back on each other in antiparallel fashion to form a loop in the tertiary structure over residues 770-856, with the loop closed by membrane-associated amphipathic alpha-helices with charged sides facing each other. We speculate that such structures could aggregate to form channels or otherwise destabilize the membrane, thereby contributing to the cytopathic effects of the gp120-gp41 complex.
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PMID:Theoretically determined three-dimensional structures for amphipathic segments of the HIV-1 gp41 envelope protein. 254 49

The crystal structure of the nucleoside 2',3'-dideoxyformycin A has been determined. The structure shows a syn conformation about the glycosidic bond, stabilised by an intramolecular hydrogen bond between the 05' and N3 atoms. HIV activity was examined in a syncytium inhibition assay. In contrast to the marked decrease in viral titre observed with 2',3'-dideoxycytidine, the formycin analogue produced no effect. It may be concluded that the syn conformation for a dideoxy nucleoside is probably deleterious to HIV inhibition of HIV replication.
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PMID:The anti-conformation of 2',3'-dideoxy nucleosides may be essential for anti-HIV activity: evidence from the crystal structure of 2',3'-dideoxy formycin A. 273 27


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