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)

The effects of three molecular weight ranges of dextran sulfate on five different human immunodeficiency virus (HIV) isolates (from patients with acquired immunodeficiency syndrome), alone and in combination with dideoxynucleosides, were investigated in vitro. The higher the molecular weight range of dextran sulfate, the more potent the activity as assessed by a quantitative syncytium formation assay. Although all five HIV isolates had similar susceptibilities to the inhibitory effects of dideoxynucleosides, the two clinical isolates of HIV (HIV type 1 [HIV-1] TM and SP) exhibited a pattern of reduced susceptibility to dextran sulfate when compared with the two cloned isolates (HIV-1 WMF and HIV-2 ROD) and a prototype laboratory strain (HIV-1 IIIB). In combination with dideoxynucleosides, the high-molecular-weight range of dextran sulfate (500,000) resulted in an antagonistic response directed against the two clinical isolates of HIV (HIV-1 TM and SP) when the antiviral concentrations of dextran sulfate were in the ineffective range. Additive or synergistic effects were seen with the other three HIV isolates and all five HIV isolates when the low-molecular-weight range of dextran sulfate (8,000) was used. The results of these studies raise issues on the impact of drug-resistant strains on disease progression and the use of dextran sulfate in combination with nucleoside analogs for the clinical management of HIV disease.
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PMID:Anti-human immunodeficiency virus effects of dextran sulfate are strain dependent and synergistic or antagonistic when dextran sulfate is given in combination with dideoxynucleosides. 229 65

An 80-kilodalton glycoprotein (gp80) was produced in human immunodeficiency virus type 2 (HIV-2)-infected cells along with three envelope glycoproteins that we have recently reported: the extracellular glycoprotein (gp125), the envelope glycoprotein precursor (gp140), and the transient dimeric form of the precursor (gp300). gp125 and gp80 were detectable after the synthesis of gp140 and the formation of gp300. Using a specific monoclonal antibody, we showed here that gp80 is a dimeric form of the transmembrane glycoprotein gp36 of HIV-2. Dimerization of the envelope glycoprotein precursor and dimeric forms of the transmembrane glycoproteins were also observed in cells infected with simian immunodeficiency virus (SIV-mac), a virus closely related to HIV-2. Under routine conditions of our experiments (i.e., extraction by 1% Triton X-100 before polyacrylamide gel electrophoresis in sodium dodecyl sulfate [SDS]), monomeric forms of the transmembrane glycoprotein of HIV-2 and SIV-mac were only seldomly observed. Dimeric forms of the envelope precursors and the transmembrane glycoproteins are probably stabilized by extraction in the nonionic detergent Triton X-100 since such dimeric forms resist dissociation during subsequent electrophoresis in the presence of the ionic detergent SDS. However, the dissociation of these dimeric forms might occur when samples are prepared by extraction directly in 1% SDS or by incubation of the purified dimers at acidic pH. Dimerization of the envelope precursor might be required for its processing to give the mature envelope proteins, whereas the transmembrane dimer might be essential for optimal structure of the virion and thus its infectivity.
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PMID:Transmembrane envelope glycoproteins of human immunodeficiency virus type 2 and simian immunodeficiency virus SIV-mac exist as homodimers. 229 88

Novel synthetic sulfated polymers, namely, sulfated polyvinyl alcohol (PVAS) and sulfated copolymers of acrylic acid with vinyl alcohol (PAVAS), proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in vitro. The compounds completely inhibited HIV-1-induced cytopathogenicity in MT-4 cells and HIV-1 antigen expression in CEM cells at a concentration of 0.8 micrograms/ml. They were equally effective against HIV-2 replication. In addition, and in contrast to azidothymidine, PAVAS and PVAS suppressed HIV-1-induced giant cell (syncytium) formation, a process that may account for the depletion of T4 lymphocytes in patients with acquired immunodeficiency syndrome. PAVAS and PVAS completely blocked giant cell formation at a concentration of 4 micrograms/ml, whereas for dextran sulfate a concentration of 100 micrograms/ml was required to achieve complete inhibition of giant cell formation. As has been demonstrated previously for the sulfated polysaccharides, the mechanism of action of PAVAS and PVAS resides in the inhibition of virus adsorption to the cells.
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PMID:Novel sulfated polymers as highly potent and selective inhibitors of human immunodeficiency virus replication and giant cell formation. 232 49

A simple, sensitive, and specific polymerase chain reaction (PCR) protocol for the detection of human immunodeficiency virus type 1 (HIV-1) is described. We have improved all three PCR steps: sample preparation, DNA amplification, and detection of the amplified product. Some of the improvements have been described previously, but they have never been combined into a complete PCR protocol. Peripheral blood mononuclear cells were lysed directly in a buffer containing sodium dodecyl sulfate, Triton X-100, and proteinase K. This crude cell lysate was amplified in a two-step PCR, first with outer primers and then with inner primers nested within the first primers. The PCR product was visualized by agarose gel electrophoresis and ethidium bromide staining. Thus, we avoided conventional DNA extraction as well as hybridization for the detection of the PCR product. The samples were analyzed with four sets of nested primers (JA4 through JA7, JA9 through JA12, JA13 through JA16, and JA17 through JA20) designed to amplify HIV-1 gag, env gp120, env gp41, and pol sequences, respectively. We were able to amplify HIV-1 sequences in all samples from 90 HIV-1-seropositive individuals with mostly mild symptoms. Of these individuals, 24 were negative in HIV-1 isolation and 9 were selected because they were infected by African and Haitian HIV-1 strains. Eighty-five (94%) individuals were positive with at least three of four primer sets. Samples from 26 healthy blood donors, as well as cells infected in vitro with human immunodeficiency virus type 2 and human T-cell leukemia virus type I, were negative in PCR, thus demonstrating the specificity of the amplification.
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PMID:Simple, sensitive, and specific detection of human immunodeficiency virus type 1 in clinical specimens by polymerase chain reaction with nested primers. 238 Mar 80

Novel sulfated polysaccharides, sulfated bacterial glycosaminoglycan (Org 31581) and chemically degraded heparin (Org 31733), have proved to be potent and selective inhibitors of human immunodeficiency virus (HIV) in vitro. Their 50% inhibitory concentrations for HIV type 1 (HIV-1) in MT-4 cells were 0.67 and 0.52 micrograms/ml, respectively. These values are comparable to those obtained for dextran sulfate and standard heparin (0.39 and 0.89 micrograms/ml, respectively). Org 31581 and Org 31733 showed much less antithrombin activity than did dextran sulfate and standard heparin. These results indicate that the anti-HIV activity of sulfated polysaccharides can be dissociated from their antithrombin activity. Org 31581 and Org 31733 were equally inhibitory to HIV-2 and HIV-1 and were also inhibitory to the replication of human cytomegalovirus. Syncytium formation, induced by cocultivation of MOLT-4 (clone 8) cells with chronically HIV-1-infected HuT 78 cells, was also inhibited by Org 31581. As previously demonstrated with dextran sulfate and heparin, both Org 31581 and Org 31733 blocked virus adsorption to the host cells. These compounds offer great promise as candidate drugs for the chemotherapy of HIV infections.
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PMID:Novel sulfated polysaccharides: dissociation of anti-human immunodeficiency virus activity from antithrombin activity. 240 68

Human immunodeficiency virus (HIV), the retrovirus that causes the acquired immunodeficiency syndrome, is cytopathic for CD4+ T cells and binds to these cells via a complex of the 110,000 m.w. viral-envelope glycoprotein, gp110, and the CD4 molecule. We treated virus with several physical, chemical, and enzymic agents to determine their effect on the capacity of HIV to bind to the CD4+ T cell line, CEM. Reduction and alkylation (but not alkylation alone) and trypsin digestion (but not glycolytic enzyme digestions) of HIV destroyed its capacity to bind. If the tertiary protein structure conferred by disulfide bonding is not disrupted, the tertiary and secondary conformations dependent on noncovalent forces appear to be thermodynamically favored, because treatment with denaturants such as sodium dodecyl sulfate, 8 M urea, alcohol, or heat (56 degrees C or 65 degrees C for 30 min) followed by removal of the denaturants did not affect binding. Irreversible denaturation and loss of binding occurred after heating at 100 degrees C for 10 min. HIV binding to CD4+ T cells was inhibited either by murine monoclonal antibodies to the CD4 molecule or by human polyclonal or murine monoclonal antibodies to the gp110 molecule. On the basis of results of binding inhibition obtained with a panel of alpha-CD4 monoclonal antibodies, the receptor site for virus on the CD4 molecule was mapped to the amino-terminal portion of the molecule. Four candidate alpha-CD4 monoclonal antibodies that were potent inhibitors of virus binding (OKT4A, OKT4D, OKT4F, and Leu-3a) were examined for the possibility that their binding sites (idiotopes) might share structural and conformational similarity with the CD4-binding site on gp110. Polyclonal human or rabbit anti-HIV sera (that reacted with gp110 and inhibited virus binding) did not react with or inhibit the binding of these four alpha-CD4 monoclonal antibodies. Conversely, rabbit anti-idiotypic sera raised against each of the four candidate CD4 monoclonal antibodies did not react with virus or inhibit virus binding to CD4+ T cells. Further search or different approaches may yet yield an idiotype that is a structural and conformational "internal image" of the CD4-binding site of virus.
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PMID:Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD4 (T4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry. 242 79

Glycyrrhizin sulfate (GLS) was synthesized and investigated for antiviral effect on the human immunodeficiency virus (HIV) in vitro in comparison with the parental anti-HIV compound glycyrrhizin (GL). In MT-4 cells after HIV infection, the virus-induced cytopathic effect and the expression of viral antigens were inhibited by 0.25 mg/ml (0.184 mM) of GLS. Moreover, GLS completely inhibited HIV-induced plaque formation in MT-4 cells at a concentration of 1 mg/ml (736 microM), the 50% inhibitory dose being 0.055 mg/ml (40 microM). GLS was found to be an efficient inhibitor of reverse transcriptase. The effect of GLS was 4 times stronger than that of GL in molar terms.
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PMID:A new anti-human immunodeficiency virus substance, glycyrrhizin sulfate; endowment of glycyrrhizin with reverse transcriptase-inhibitory activity by chemical modification. 244 73

The polyanionic substances dextran sulfate and heparin were investigated for their antiviral effect on the human immunodeficiency virus (HIV) in vitro. Dextran sulfate and heparin effected a 50% reduction in the cytopathogenicity of HIV for MT-4 cells at a concentration of 4.7 and 7.5 micrograms/ml, respectively. In Molt-4 (clone 8) cells, these values were slightly higher (14.1 and 15.6 micrograms/ml, respectively). No toxicity for the host cells was noted with these compounds at a concentration up to 400 micrograms/ml, so that the selectivity indexes, as based on the ratio of the 50% cytotoxic dose to the 50% antiviral effective dose, were well in excess of 100. These findings may have far reaching implications both diagnostically, when attempts are made to isolate HIV from heparinized blood samples, as therapeutically, to the extent that dextran sulfate or heparin may be useful in blocking HIV replication in vivo.
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PMID:Inhibitory effect of dextran sulfate and heparin on the replication of human immunodeficiency virus (HIV) in vitro. 244 84

The inhibitory effects of several polysaccharides, dextran, xylofuranan, and ribofuranan, and their sulfated counterparts on the infectivity and replication of human immunodeficiency virus (HIV) were examined by using an HTLV-I-carrying cell line, MT-4, in vitro. Dextran sulfate (Mw 34 X 10(3], xylofuranan sulfate, and ribofuranan sulfate completely prevented HIV-induced cytopathic effects (CPE) at concentrations greater than 10 micrograms/ml and dextran sulfate (Mw 7 X 10(3] at concentrations greater than 100 micrograms/ml. However, the non-sulfated compounds did not prevent them at any concentration tested. The anti-HIV effect of these polysaccharides was confirmed by measuring HIV-specific antigen expression in infected MT-4 cells. In cocultures with MOLT-4 and MOLT-4/HIVHTLV-IIIB cells, formation of multinucleated cells was completely inhibited in the presence of 100 micrograms/ml of these sulfated compounds. Dextran sulfate showed 20-30% growth inhibition of uninfected MT-4 cells at 1000 micrograms/ml but dextran sulfate, xylofuranan sulfate, and ribofuranan sulfate showed no effect on sulfated polysaccharides efficiently inhibited the reverse transcriptase activity of avian myeloblastosis virus and HIV.
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PMID:Sulfation of polysaccharides generates potent and selective inhibitors of human immunodeficiency virus infection and replication in vitro. 244 45

A new reverse transcriptase (RT) inhibitor was extracted and purified from the red alga Schizymenia pacifica. The chromatographic behavior and chemical properties of this sea algal extract (SAE) suggest that it is a sulfated polysaccharide having a molecular weight of approximately 2,000,000. SAE is composed of galactose (73%), sulfonate (20%), and 3,6-anhydrogalactose (0.65%). SAE is a member of the lambda-carrageenan family, based on its infrared spectrum and products of hydrolysis. SAE selectively inhibited human immunodeficiency virus (HIV) RT and replication in vitro. When MT-4 cells were treated with more than 10(4) inhibitory units (IU) of SAE per ml after HIV infection, significant inhibition of viral antigen synthesis was observed. Furthermore, more than 90% of cells were viable in the cultures exposed to 4 X 10(4) to 8 X 10(4) IU of SAE per ml, while almost all the MT-4 cells in the control culture had died by 10 days after HIV infection. The inhibitory effect of SAE on HIV replication was confirmed by plaque reduction assays. The 50% inhibitory dose of SAE was 9.5 x 10(3) IU/ml. Chondroitin sulfate A, dermatan sulfate, heparan sulfate, keratan polysulfate, and heparin also inhibited the RT of avian myeloblastosis virus. SAE immediately inhibited RT activity when added to an assay mixture after the start of the reaction.
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PMID:Purification and characterization of an avian myeloblastosis and human immunodeficiency virus reverse transcriptase inhibitor, sulfated polysaccharides extracted from sea algae. 244 20


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