Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the course of investigating effective biological active substances, we detected a substance in an extract of silkworm faeces that markedly suppresses viral production. The extract, prepared with hot phosphate-buffered saline and purified with ammonium sulfate precipitation, inhibited HVJ (Sendai virus), HSV (herpes simplex virus type-1), and HIV (human immunodeficiency virus type-1), but not poliovirus, suggesting that it is effective on enveloped virus production but not on non-enveloped ones. In the case of HVJ, indirect immunofluorescent staining using anti-HVJ antibody and Northern blotting analysis showed that, while viral adsorption and entry into the host cells were not affected, the synthesis of viral specific gene was inhibited by pretreatment of the virions with the extract. The extract affected more effectively aged virion, which losses membrane function as barrier and its envelope is leaky, than young virion that maintains barrier function. The active substance was partially purified by gel filtration after treatment of the extract with 1 N NaOH solution. From analysis with SDS-PAGE (SDS-polyacrylamide gel electrophoresis), protein bands were detected with molecular masses of about 25 kDa and near 14 kDa, while sugars were also detected with lectin blotting.
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PMID:Suppression of enveloped virus production with a substance from silkworm faeces. 907 8

Nef is a 27 kDa myristylated phosphoprotein expressed early in infection by HIV. The N terminus of Nef is thought to play a vital role in the functions of this protein through its interactions with membrane structures. The solution structure of a 25-residue polypeptide corresponding to the N terminus of Nef (Nef1-25) has been investigated by 1H NMR spectroscopy. In aqueous solution at pH 4.8 and 281 K, this peptide underwent conformational averaging, with Pro13 existing in cis and trans conformations in nearly equal proportions. In methanol solution, however, the peptide adopted a well-defined alpha-helical structure from residues 6 to 22, with the N- and C-terminal regions having a less ordered structure. On the basis of a comparison of chemical shifts and NOEs, it appeared that this helical structure was maintained in aqueous trifluoroethanol (50% v/v) and to a lesser extent in a solution of SDS micelles. When the N-acetyl group was replaced by either an N-myristyl or a free ammonium group, there was little effect on the three-dimensional structure of the peptide in methanol; deamidation of the C terminus also had no effect on the structure in methanol. In water, the myristylated peptide aggregated. The similarity between the sequences of Nef1-25 and melittin is reflected in the similar structures of the two molecules, although the N-terminal helix of melittin is more defined. This similarity in structure raises the possibility that Nef1-25 not only interacts with membranes but also may be capable of disrupting them and causing cell lysis. This type of interaction could contribute at least in part to the killing of bystander cells in lymphoid tissues during HIV infection.
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PMID:Solution structure of a polypeptide from the N terminus of the HIV protein Nef. 916 67

Human immunodeficiency virus type 1 (HIV-1) normally enters cells by direct fusion with the plasma membrane. In this report, HIV-1 particles capable of infecting cells through an endocytic pathway are described. Chimeric viruses composed of the HIV-1 core and the envelope glycoprotein of vesicular stomatitis virus (VSV-G) were constructed and are herein termed HIV-1(VSV) pseudotypes. HIV-1(VSV) pseudotypes were 20- to 130-fold more infectious than nonpseudotyped HIV-1. Infection by HIV-1(VSV) pseudotypes was markedly diminished by ammonium chloride and concanamycin A, a selective inhibitor of vacuolar H+ ATPases, demonstrating that these viruses require endosomal acidification to achieve productive infection. HIV-1 is thus capable of performing all of the viral functions necessary for infection when entry is targeted to an endocytic route. Maximal HIV-1 infectivity requires the presence of the viral Nef protein and the cellular protein cyclophilin A (CyPA) during virus assembly. Pseudotyping by VSV-G markedly suppressed the requirement for Nef. HIV-1(VSV) particles were also resistant to inhibition by cyclosporin A; however, the deleterious effect of a gag mutation inhibiting CyPA incorporation was not relieved by VSV-G. These results suggest that Nef acts at a step of the HIV-1 life cycle that is either circumvented or facilitated by targeting virus entry to an endocytic pathway. The findings also support the hypothesis that Nef and CyPA enhance HIV-1 infectivity through independent processes and demonstrate a mechanistic difference between reduction of HIV-1 infectivity by cyclosporin A and gag mutations that decrease HIV-1 incorporation of CyPA.
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PMID:Pseudotyping human immunodeficiency virus type 1 (HIV-1) by the glycoprotein of vesicular stomatitis virus targets HIV-1 entry to an endocytic pathway and suppresses both the requirement for Nef and the sensitivity to cyclosporin A. 922 76

Two per cent glutaraldehyde is the most commonly used disinfectant in endoscopy units within the UK. Unfortunately adverse reactions to glutaraldehyde are common among endoscopy personnel and the Health and Safety Commission has recommended substantial reductions in atmospheric levels of glutaraldehyde in order to comply with the Control of Substances Hazardous to Health Regulations, 1994. The Working Party addressed ways of eliminating or minimising exposure to glutaraldehyde in endoscopy units by reviewing alternative disinfectants and the use of automated washer/disinfectors. Alternatives to glutaraldehyde must be at least as microbicidal as glutaraldehyde, non-irritating and compatible with endoscope components and decontamination equipment. Peracetic acid is a highly effective disinfectant and may be a suitable alternative to glutaraldehyde. Peracetic acid has a vinegary-like odour and is claimed to be less irritating than glutaraldehyde. Experience with this agent remains relatively limited and the Working Party recommends that peracetic acid should be used in sealed or exhaust ventilated facilities until further experience is obtained. It is considerably more expensive than glutaraldehyde, is less stable and large volumes have to be stored. It causes cosmetic (but not functional) damage to endoscopes and is not compatible with some washer/ disinfectors. Chlorine dioxide is a powerful oxidising agent and highly effective as a disinfectant. Once activated it must be stored in sealed containers with little head space. Fumes cause irritation and sealed or exhaust ventilated facilities are necessary. The agent may damage some metallic and polymer components of endoscopes and automated washer/disinfectors and compatibility should be established with equipment manufacturers before the agent is used. Other disinfectants such as peroxygen compounds and quaternary ammonium derivatives are less suitable because of unsatisfactory mycobactericidal and/or virucidal activity, or incompatibility with endoscopes and automated washer/disinfectors. Alcohol is effective but, on prolonged contact, is damaging to lens cements. It is also flammable and therefore unsuitable for use in large quantities in automated systems. Superoxidised water (Sterilox) is an electrochemical solution (anolyte) containing a mixture of radicals with strong oxidising properties. It is highly microbicidal when freshly generated, provided items are thoroughly clean and strict generation criteria are met--that is, current, pH, redox potential. It seems to be safe for users and provided field trials substantiate laboratory efficacy tests, and the agent is non-damaging, it too may become an alternative to glutaraldehyde. When 2% glutaraldehyde is used for manual and automated disinfection, 10 minutes' immersion is recommended for endoscopes before the session and between patients. This will destroy vegetative bacteria and viruses (including hepatitis B virus (HBV) and HIV). A five minute contact period is recommended for 0.35% peracetic acid and for chlorine dioxide (1100 ppm av ClO2), but if immersed for 10 minutes sporicidal activity will also be achieved. At the end of each session 20 minutes' immersion in glutaraldehyde or five minutes in peracetic acid or chlorine dioxide is recommended. Microbiological studies show that 20 minutes of exposure to 2% glutaraldehyde destroys most organisms, including Mycobacterium tuberculosis. The Working Party concludes therefore that immersion of the endoscope in 2% glutaraldehyde for 20 minutes is sufficient for endoscopy involving patients with AIDS and other immunodeficiency states or pulmonary tuberculosis. Similarly, 20 minutes' immersion is recommended at the start of the list and between cases for endoscopic retrograde cholangiopancreatography (ERCP) when high level disinfection is required. Cleaning and disinfection of endoscopes should be undertaken by trained staff in a dedicated room. Thorough cleaning with detergent
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PMID:Cleaning and disinfection of equipment for gastrointestinal endoscopy. Report of a Working Party of the British Society of Gastroenterology Endoscopy Committee. 961 26

Heparins/heparan sulfates modulate the function of proteins and cell membranes in numerous biological systems including normal and disease processes in humans. Heparin has been used for many years as an anticoagulant, and anticoagulant heparin-mimetics were developed several decades ago by chemical sulfation of non-mammalian polysaccharides, e.g., an antithrombotic sulfated xylan. This pharmaceutical, which comprises a mixture of sulfated oligoxylans, also mimics most other biological actions of natural heparins in vitro, including inhibition of the human immunodeficiency virus, but the molecular basis for these actions has been unclear. Here, numerous Components of the sulfated oligoxylan mixture were isolated and when bioassayed in the case of anti-HIV-1 infectivity revealed that a structural specificity underlines the capacity of sulfated xylan to inhibit HIV-1, rather than a non-specific mechanism. Components were isolated by chromatographic fractionation through Bio-Gel P10 in 0.5 M ammonium bicarbonate. This fractionation revealed an elution range associated with apparent molecular weights of approximately 22000 to <1500 relative to standard heparin and heparan sulfates and newly prepared sulfated oligosaccharide standards. Components were characterized by metachromatic absorption spectroscopy, ultracentrifugation, GlcA analysis, and potency against HIV-1 infectivity, both in the tetrazolium cytotoxicity assay and in syncytium-forming assays, in CD4-lymphocytes. Structural specificity was indicated by the differential potencies exhibited by the Components: Highest activity (cytotoxicity) was exhibited by Components in the chromatographic region > or = approximately 5500 in mass (50% effective (inhibitory) concentration = 0.5-0.7 microg ml(-1) in the first fractionation series, and 0.1-0.5 microg ml(-1) in a second series). The potency declined sharply below approximately 5400 in mass, but with an exception; a second structure exhibiting relatively high potency eluted among low-mass oligosaccharides which had an average size of approximately a nonomer. Components displayed differential potencies also against the syncytium-forming infectivity of HIV-1. The high potency against syncytium-formation was retained by Components down to a minimum size of about 4500 in mass, smaller than the > or = approximately 5400 required above. One in ten of the beta1,4-linked xyloses in the native xylan are substituted with a monomeric alpha1,2 DGlcA branch. We have speculated that pharmaceutical actions of sulfated xylan might be related to structures involving the alpha-D linked substituents and this was examined using a space-filling model of a sulfated octaxylan and by analyses of Components for GlcA content. Understanding structure/function relations in the heparin-like actions of these agents would be of general significance for the careful examination of their potential clinical usefulness in many human processes modulated by heparins, including AIDS.
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PMID:Structure-function relations of heparin-mimetic sulfated xylan oligosaccharides: inhibition of human immunodeficiency virus-1 infectivity in vitro. 988 76

The effect of 44 different metal ions (Ag+, Al3+, As(O-)2, Au3+, Ba2+, Be2+, Bi3+, Cd2+, Ce3+, CO2+, Cr(O2-)4, Cr3+, Cs+, Cu2+, Fe3+, Fe2+, Ga3+, Ge4+, Hg2+, Ir4+, La3+, Li+, Mn2+, MO6+, Ni2+, OS4+, Pb2+, Pt4+, Rb+, Rh3+, Sb5+, Se(O2-)4, Se(O2-)3, Sn2+, Sr2+, Th4+, T1+, U(O2+)2, V(O-)3, VO2+, W(O2-)4, Y3+, Zn2+, and Zr4+) on the activity of the reverse transcriptase (RT) of the human immunodeficiency virus (HIV-1) was investigated in vitro. For this study, the RT activity assay was carried out by means of an enzyme-linked immunosorbent assay (ELISA) kit, using the template/primer hybrid poly(A) oligo(dT)15, which required some modifications: (1) possible interfering metal chelators (such as EDTA) in the original lysis buffer were avoided, and a new buffer (50 mM Tris-NO3, pH 7.8) was used throughout; (2) an amount of 2 ng of RT per well was considered to be optimal after checking the linearity of the reaction with increasing amounts of enzyme; (3) an incubation temperature of 37 degrees C and an incubation time of 1 h were chosen after preliminary studies in a wide range of temperature and time. At an incubation temperature > or = 40 degrees C, there was a dramatic loss of enzymatic activity. In addition, when RT alone was preincubated for 1 h at 5 degrees C, 25 degrees C, and 37 degrees C, there was a large (83%) loss of activity at 37 C as compared to that at 5 degrees C. These results are indicative of enzyme thermolability, which is higher in the absence of substrates. The effect of metal ions on RT activity was tested using two different metal salt concentrations (10(-4) M and 10(-5) M). Under such experimental conditions, the presence of five metal ions (Pt4+, Ag+, Rh3+, Zn2+, and Hg2+) decreased the RT activity in a dose-response fashion. The observed order of effectiveness with respect to inhibition was Pt4+ > Ag+ > Rh3+ > Zn2+ = Hg2+. Estimated mean inhibitory concentrations (IC50) were 7.8 microM for (NH4)2PtCl6, 14.1 microM for AgNO3, 46.8 microM for RhCl3, 53.7 microM for Zn(SO)4, and 56.2 microM for Hg(NO3)2. Because these data are of the same order of magnitude as the corresponding values related to other RT inhibitors used in anti-AIDS therapy, metal compounds or their derivatives could give an interesting contribution in the development of new RT inhibitors for clinical use.
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PMID:Effects of trace metal compounds on HIV-1 reverse transcriptase: an in vitro study. 1032 22

Covalent linkage of the arginine-rich fragment of the Tat protein to 1,4,7,10-tetraazacyclododecane (cyclen) results in the selective cleavage of the TAR-RNA of HIV-1 (see picture; the biotin at the 5' end acts as a label for the subsequent analysis of the cleavage fragments). The cleavage occurs at room temperature and is diminished when Eu(III) ions are present-at a concentration of about 1/10 of the concentration of the peptide-cyclen conjugate. The pH dependence indicates that two ammonium ions are responsible for the cleavage reaction. The white arrows in the schematic diagram mark the cleavage sites in RNase T1, and the black arrows the sites in the peptide-cyclen conjugate.
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PMID:Selective Cleavage of the HIV-1 TAR-RNA with a Peptide-Cyclen Conjugate. 1042 97

Apoptosis has been indicated as a mechanism of T cell depletion in HIV-infected subjects and useful in monitoring disease progression. We investigated for the presence of apoptotic T lymphocytes in 130 HIV subjects in various stages of disease by the newly developed cell permeant DNA dye Apostain. Blood was collected in EDTA, lysed in buffered ammonium chloride, fixed in freshly prepared 1% paraformaldehyde and stored in aliquots at -80 degrees C. Samples were thawed and double stained with FITC conjugated-CD3 monoclonal antibody and Apostain. Flow cytometry was then performed and T cells gated on a CD3 versus side scatter dot plot. Normal samples treated in the same manner served to establish the boundary separating non-apoptotic from apoptotic cells. There was no statistically significant association between the proportion of subjects with detectable apoptotic cells and CDC clinical categories A, B and C at the time of admission to the study, although a trend toward a lower apoptotic rate in category A (A= 29%, B=40% and C=41%) was noticed. Conversely, CDC T cell categories 2 and 3 contained significantly higher proportions of Apostain positive patients (1=6%, 2=32% and 3=49%, P=0.072, by chi(2) test). Most importantly, Apostain test identified subjects at risk of disease progression during a 3.5-7 months follow-up in CDC category B and 2 (P=0.008 and P=0.0003, by Fisher's exact test, respectively). A similar, albeit not statistically significant trend was observed also in the other categories. Not requiring extensive manipulation of fresh samples nor cumbersome culture techniques, Apostain test appears suitable for identifying HIV subjects at higher risk of disease progression in clinical settings.
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PMID:Detection of apoptotic T lymphocytes in peripheral blood of human immunodeficiency virus (HIV)-infected subjects by apostain. 1067 45

The search for new small-molecule CCR5 antagonists by high-throughput screening (HTS) of the Takeda chemical library using [(125)I]RANTES and CHO/CCR5 cells led to the discovery of lead compounds (A, B) with a quaternary ammonium or phosphonium moiety, which were synthesized to investigate new MCP-1 receptor antagonists. A series of novel anilide derivatives 1 with a quaternary ammonium moiety were designed, synthesized, and tested for their CCR5 antagonistic activity. Through the optimization of lead compounds, we have found N,N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6, 7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]tetrahydr o-2 H-pyran-4-aminium chloride (1r, TAK-779) as a highly potent and selective nonpeptide CCR5 antagonist with a IC(50) value of 1.4 nM in the binding assay. Compound 1r also inhibited the replication of macrophage (M)-tropic HIV-1 (Ba-L strain) in both MAGI-CCR5 cells and PBMCs with EC(50) values of 1.2 and 3.7 nM, respectively. The synthesis and structure-activity relationships of 1r and its related compounds are detailed.
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PMID:Discovery of novel, potent, and selective small-molecule CCR5 antagonists as anti-HIV-1 agents: synthesis and biological evaluation of anilide derivatives with a quaternary ammonium moiety. 1082 17

Recombinant HIV-1 p66 (rp66, a subunit of reverse transcriptase (RT), a heterodimer of p66 and p51) was produced in Escherichia coli in three different ways. First, rp66 was produced as a part of the fusion protein of lacZ protein and HIV-1 pol protein consisting of three components: protease (p10), RT (p51/p66), and integrase (p31), and was released from the fusion protein by the protease (pol-rp66). Second, rp66 with Ser-Ser at the N-terminus was produced as a fusion protein with maltose-binding protein containing a factor Xa site between the two proteins (MBP-Ser-Ser-rp66) and was released from the fusion protein by factor Xa (Ser-Ser-rp66). Third, rp66 with Met-Gly at the N-terminus was produced in transformed cells (Met-Gly-rp66). The recombinant proteins were purified from sonic extracts of transformed cells by ammonium sulfate fractionation and various column chromatographies. MBP-Ser-Ser-rp66 and Met-Gly-rp66 were readily purified in sufficient amounts for labeling with 2, 4-dinitrophenyl groups and beta-D-galactosidase from E. coli, but pol-rp66 and Ser-Ser-rp66 were not for enzyme-labeling. Ser-Ser-rp66 was not only polymerized but also degraded to considerable extents. The purified preparations were labeled with 2,4-dinitrophenyl groups and beta-D-galactosidase and were tested in immune complex transfer enzyme immunoassay of antibody IgG to HIV-1 RT using serum samples from 600 HIV-1 seronegative and 30 HIV-1 seropositive subjects. Among various combined uses of the two labeled preparations, the uses of 2,4-dinitrophenylated MBP-Ser-Ser-rp66 and pol-rp66 with beta-D-galactosidase-labeled Met-Gly-rp66 showed the highest (99.8%) and the second highest (99.5%) specificities, which were higher than that with the labeled preparations used in the previous study (98. 0%).
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PMID:Preparations of recombinant HIV-1 p66 antigen to improve the specificity of immune complex transfer enzyme immunoassay of antibody IgG to HIV-1 reverse transcriptase. 1090 70


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