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)

Various polyoxometalates proved inhibitory to the replication of a number of enveloped DNA and RNA viruses, i.e., herpesviruses (herpes simplex and cytomegalo), togaviruses (Sindbis), paramyxoviruses (respiratory syncytial), rhabdoviruses (vesicular stomatitis), arenaviruses (Junin and Tacaribe), and retroviruses [human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), simian immunodeficiency virus, and murine sarcoma virus]. The most potent compounds, i.e., JM1590 [K13[Ce(SiW11O39)2]. 26H2O] and JM2766 [K6[BGa(H2O)W11O39]. 15H2O], inhibited HIV-1 and simian immunodeficiency virus at concentrations as low as 0.008-0.8 microM. The polyoxometalates also inhibited giant cell formation in co-cultures of HIV-infected HUT-78 cells and uninfected MOLT-4 cells. Studies designed to unravel the mechanism of action of these compounds revealed that they inhibit the reverse transcriptase activity associated with HIV. The polyoxometalates also proved inhibitory to the binding of HIV-1 virions to the cells. From "time of addition" experiments, whereby the polyoxometalates were added at different times after virus infection, their mechanism of anti-HIV action could be attributed to inhibition of virus-cell binding. There was a good correlation (r = 0.84) between the inhibitory effects of the compounds on HIV-1-induced cytopathicity and their inhibitory effects on syncytium formation and a close correlation (r = 0.902) between their inhibitory effects on syncytium formation and their interaction with gp120, whereas there was no correlation between their anti-HIV-1 activity and their inhibitory effects on HIV-1 reverse transcriptase. In flow cytometric studies, the compounds did not interfere with the binding of OKT4A/Leu-3a monoclonal antibody to the CD4 receptor of uninfected cells, but they inhibited binding of anti-gp120 monoclonal antibody to HIV-1-infected cells. Thus, the binding of the polyoxometalates to the viral envelope glycoprotein gp120 is responsible for their anti-HIV activity.
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PMID:Mechanism of anti-human immunodeficiency virus action of polyoxometalates, a class of broad-spectrum antiviral agents. 128 64

The drug Ro5-3335 [7-chloro-5-(2-pyrryl)-3H-1,4-benzodiazepin-2(H)-one] inhibits human immunodeficiency virus type 1 (HIV-1) gene expression at the transcriptional level through interference with Tat-mediated transactivation (M.-C. Hsu, A. D. Schutt, M. Holly, L. W. Slice, M. I. Sherman, D. D. Richman, M. J. Potash, and D. J. Volsky, Science 254:1799-1802, 1991). We confirmed this specific inhibitory effect in a quantitative bioassay based on transactivation of a chimeric gene comprising the HIV-1 long terminal repeat promoter fused to the lacZ gene of Escherichia coli and transfected in a HeLa cell line expressing Tat. Ro5-3335 was found to inhibit HIV-1 long terminal repeat-driven lacZ gene expression at a 50% inhibitory concentration of 0.5 microM. The in vitro anti-HIV-1 activity of Ro5-3335 was highly dependent on the nature of the host cells. The highest selectivity index, 50, was found in phytohemagglutinin-stimulated peripheral blood lymphocytes. The selectivity index was between 1 and 10 in the CD4+ T-cell lines CEM, MOLT-4 (clone 8), and HUT-78. In MT-4 and MT-2 cells, Ro5-3335 had no inhibitory effect on HIV-1 replication. The absence of anti-HIV-1 activity of Ro5-3335 in MT-4 cells was confirmed by using different parameters of virus replication and different multiplicities of infection. In persistently HIV-1-infected HUT-78/IIIB/LAI cells, Ro5-3335 failed to demonstrate any activity at subtoxic concentrations. The cytotoxicity of Ro5-3335 was significantly lower in peripheral blood lymphocytes than in the CD4+ T-cell lines.
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PMID:Cell type-specific anti-human immunodeficiency virus type 1 activity of the transactivation inhibitor Ro5-3335. 128 90

Transmission of human T cell leukemia virus type I (HTLV-I) to a T cell line (MOLT-4#8) was studied using cell-free virus infection or cocultivation with an HTLV-I-transformed T cell line (MT-2). Immunofluorescence and FACS analyses showed that HTLV-I was efficiently adsorbed onto MOLT-4#8 cells. However, after adsorption, no extrachromosomal viral DNA in the cells was detected by the Southern blot method. In contrast, when MT-2 cells were cocultured with MOLT-4#8 cells, generation of extrachromosomal DNA was clearly observed. These data suggest that the cell-free HTLV-I may have difficulties in penetration, uncoating or reverse transcription. After cocultivation, MOLT-4#8 cells chronically infected with HTLV-I were cloned and analyzed. Only four provirus-positive cell lines were obtained. The transmission rate of the virus by cocultivation seemed to be low in our experimental system, although marked cell fusion was observed. Moreover, none of the cloned cell lines which harbored HTLV-I provirus expressed any viral protein. Inefficient integration and expression of the provirus might be hypothesized as compared with human immunodeficiency virus type 1 transmission.
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PMID:Inefficient transmission of HTLV-I to MOLT-4 cells by cell-free virus and cocultivation. 130 3

1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) and E-5-(2-bromovinyl)uracil, a metabolite of BV-araU, did not affect either the anti-human immunodeficiency virus activity or the cytotoxicity of azidothymidine in MT-4 and MOLT-4 cells. Similarly, the bromovinyl compounds did not affect the in vitro antitumor activities of arabinosylcytosine, 5-fluorouracil, and 5-fluoro-2'-deoxyuridine. The anti-varicella-zoster virus activity of BV-araU was not influenced by azidothymidine, 2',3'-didehydro-2',3'-dideoxythymidine, or arabinosylcytosine, whereas relatively high concentrations of fluorinated antitumor agents enhanced the anti-varicella-zoster virus activity.
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PMID:In vitro drug combination of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil with anti-human immunodeficiency virus or anticancer nucleosides. 131 47

We have previously reported the potent stimulation effect of lignin on the iodination of myeloperoxidase (MPO)-positive cells. We investigated here the anti-HIV (human immunodeficiency virus) activity of lignins in the MPO-positive (HL-60) and -negative (U-937) human myelogenous leukemic cell lines. Natural lignified material and dehydrogenation polymers, but not their precursors, effectively inhibited the cytopathic effect of HIV infection in both these cells as well as in MT-4 and MOLT-4 cells. HIV infection caused significant reduction of MPO activity in HL-60 cells, regardless of the presence or absence of lignins. These data suggest that MPO might not be involved in the anti-HIV activity induction by lignins.
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PMID:Effect of lignins on HIV-induced cytopathogenicity and myeloperoxidase activity in human myelogenous leukemic cell lines. 133 79

Syncytia or multinucleated giant-cell formation is one of the major cytopathic effects induced by human immunodeficiency virus (HIV) infection. Cell fusion results from the strong interaction of CD4 molecules on the surface of the uninfected T cells and gp120, an external envelope glycoprotein of HIV on the infected T cells. We studied the production of HIV in fusion cells between MOLT-4 and virus-infected MOLT-4/HIV cells and found that HIV production was enhanced up to three- to fivefold, which showed a good correlation with the appearance and extent of syncytia formation. Blocking the fusion by monoclonal antibody against a binding epitope of CD4 molecule to gp120 decreased the HIV production significantly. Enhancement of HIV production was observed by more than five-fold in comparison with chronically infected cells, which were fusion free 20 hr postcocultivation. Electron microscopic observation also showed the presence of abundant HIV particles inside the fused cells and on the outer surface. AZT blocked the HIV augmentation of fused cells in coculture completely. Southern blot analysis revealed that both integrated and unintegrated HIV DNA were highly accumulated in fusion cells, as compared with fusion-free MOLT-4/HIV cells. Among unintegrated DNA, circular and linear DNA were accumulated to a similar degree. Northern blot hybridization showed that rapid enhancement of all three species of HIV-specific RNA containing genomic (9.2 kb) and subgenomic (4.3 and 1.9 kb) RNAs were found 20 hr postinfection in fusion cells. These data suggest that syncytia formation is an extremely active infection process of HIV, by which multiple rounds of reinfection might take place.
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PMID:Increased production of human immunodeficiency virus (HIV) in HIV-induced syncytia formation: an efficient infection process. 134 63

A sodium hydroxide extract from cacao husk inhibited the cytopathic effect of human immunodeficiency virus type 1 (HIV-1) against HTLV-1-transformed T-cell lines MT-2 and MT-4. It also inhibited syncytium formation between HIV-infected and uninfected lymphoblastoid T-cell line, MOLT-4. The anti-HIV activity was concentrated by membrane filter fractionation to a fraction with molecular weight of 100-300 KDa. Anti-HIV activity of the extract was attributable to interference with the virus adsorption, rather than to inhibition of the virus replication after adsorption.
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PMID:Effect of cacao husk extract on human immunodeficiency virus infection. 136 48

Contact of human immunodeficiency virus (HIV)-infected MOLT-4 lymphocytes with epithelial cells derived from small intestine (I407; Intestine 407) resulted in a rapid polar budding of viral particles into an enclosed space formed by interdigitating microvilli of the contacting cells. Electron microscopy showed that released HIV was taken up into the mucosal cell via three independent mechanisms: (1) phagocytosis, (2) coated pits, and (3) direct fusion. Morphological evidence suggests that internalized HIV may escape into the cytoplasm of the target cell by uncoating at the endosomal membrane. Based on CD4 antibody binding and CD4 antibody blocking experiments, HIV entry does not appear to be mediated by a viral CD4 receptor. Productivity of I407 infection was confirmed by virus isolation from cocultured MT-4 lymphocytic cells, reverse transcriptase assay, p24 antigen ELISA, in situ HIV mRNA hybridization, and Southern dot blot analysis. Contrary to infection with free virus, the cell-to-cell infection was not blocked by anti-gp120 or antiviral serum from HIV-positive individuals. It appears that HIV transmission within the confined space between contacting cells enables HIV to evade immune protection provided by neutralizing antibodies. Our results reveal a mechanism of HIV infection of epithelial cells which is triggered by cell-cell contact. Furthermore, these observations offer an insight into the cellular sequence of events which may take place during sexual transmission of HIV across an intact epithelial barrier.
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PMID:Mechanism of HIV spread from lymphocytes to epithelia. 137 Jan 28

More than 40 peptides associated with tachyplesin and polyphemusin, which are highly abundant in hemocyte debris of the horseshoe crabs Tachypleus tridentatus and Limulus polyphemus, were synthesized. Among these peptides, we found that a novel compound, which was called T22 ([Tyr-5,12, Lys-7]polyphemusin II), strongly inhibited the human immunodeficiency virus type 1 (HIV-1)-induced cytopathic effect and viral antigen expression. Its 50% effective concentration was 0.008 micrograms/ml, while its 50% cytotoxic concentration was 54 micrograms/ml. The anti-HIV activity of T22 was observed with several strains of HIV-1, including zidovudine-resistant strains, and with HIV-2 within the concentration range of 0.006 to 0.071 microgram/ml. T22 efficiently inhibited giant cell formation on the cocultivation of MOLT-4/HIV and MOLT-4 cells but modestly inhibited direct HIV binding. T22 did not inhibit reverse transcriptase activity. A time-of-addition study, which involved monitoring of the appearance of proviral DNA by using the polymerase chain reaction technique, found that T22 exerted its effect on a process, most probably virus-cell fusion or uncoating, immediately after virus adsorption.
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PMID:Anti-human immunodeficiency virus activity of a novel synthetic peptide, T22 ([Tyr-5,12, Lys-7]polyphemusin II): a possible inhibitor of virus-cell fusion. 138 24

The effects of human interferon-alpha (IFN-alpha) or maltose-stabilized IFN-alpha (MS-IFN-alpha) on IL-2 production by PHA- or anti-CD3 mAb-stimulated MOLT 16 cells, a human leukemic T cell line, were studied. MS-IFN-alpha is an IFN-alpha-containing powder in which maltose was used as an excipient, and has been shown to have a positive effect on human immunodeficiency virus (HIV)-infected patients. In this study, MS-IFN-alpha powder was dissolved in a culture medium and used for the experiments. IL-2 production by PHA- or anti-CD3 mAb-stimulated MOLT 16 cells was augmented by coculturing with IFN-alpha or MS-IFN-alpha. The augmentation of IL-2 production by IFN-alpha or MS-IFN-alpha was completely abrogated by rabbit anti-IFN-alpha antibody. We have previously shown that IL-2 production by PHA-stimulated MOLT 16 cells is augmented by coculturing with IL-1. Furthermore, IL-2 production by PHA-stimulated MOLT 16 cells was also augmented by human TNF-alpha in a dose-dependent manner. The TNF-alpha-induced augmentation was completely abrogated by rabbit anti-TNF-alpha antibody. Interestingly, both IFN-alpha and MS-IFN-alpha synergized with rIL-1 alpha or TNF-alpha resulting in IL-2 production being augmented far more effectively than either cytokine alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The immunomodulatory role of IFN-alpha or maltose-stabilized IFN-alpha on T-cell activation. 142 Jun


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