Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Levels of human immunodeficiency virus (HIV) DNA, RNA, or p24 antigen and reverse transcriptase activity in T-cell cultures treated with 500 IU of recombinant alpha interferon (rIFN alpha) per ml were comparable to those in control cultures. Radioimmunoprecipitation analysis of proteins in lysates of IFN-treated T cells documented a marked accumulation of HIV proteins. Localization of gp120 by immunofluorescence showed a diffuse pattern in IFN-treated cells quite distinct from the ring pattern in untreated control cells. That large quantities of gp120 in aberrant cell compartments might affect HIV morphogenesis was confirmed in infectivity studies: virions from IFN-treated cells were 100- to 1,000-fold less infectious than an equal number of virions from control cells. Direct examination of IFN-treated and control HIV-infected cells by transmission electron microscopy showed little difference in the number or distribution of viral particles. However, quantitation of gp120 by immunogold particle analysis revealed a marked depletion of envelope glycoprotein in virions released from IFN-treated cells. This defect in gp120 assembly onto mature viral particles provides a molecular basis for this loss of infectivity.
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PMID:Loss of infectivity by progeny virus from alpha interferon-treated human immunodeficiency virus type 1-infected T cells is associated with defective assembly of envelope gp120. 127 6

Human immunodeficiency virus (HIV-1) isolates from 8 Ethiopian and 8 Swedish AIDS patients, none of them treated with antiviral drugs, were compared for sensitivity to azido-deoxy-thymidine (AZT), dideoxy-inosine (ddI) and interferon-alpha. HIV was isolated from peripheral blood mononuclear class, identified by Western blot and nucleotide sequencing, and passaged 1-3 times. Sensitivity to the 3 drugs, expressed as ED50s relative to positive controls, was determined by culturing HIV in the presence of drugs in a range of concentrations and assaying the supernatant for p24 antigen and the virus pellet for reverse transcriptase (RT). Dose-dependent anti-HIV activity for AZT was seen in the 8 Ethiopian isolates, and ED50s for p24 antigen and RT activity were correlated. 1 Ethiopian HIV isolate was sensitive to ddI, and another, to interferon-alpha. 1 Swedish HIV was resistant to AZT, and on analysis had a mutation from threonine to tyrosine at position 215. There were no significant differences between ED50s for interferon in the Swedish and Ethiopian HIVs. Combined data for each drug showed correlation between the p24 antigen and RT activities of the Ethiopian and Swedish HIVs. Since there was no resistance observed in the Ethiopian HIV to AZT or ddI, low-dose treatment would probably slow progression of HIV infection in Ethiopians, if these drugs could be made available for clinical trials.
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PMID:Response of Ethiopian human immunodeficiency virus type 1 isolates to antiviral compounds. 128 93

Human monocytes stimulated with phorbol 12-myristate 13-acetate or opsonized zymosan in vitro were viricidal to human immunodeficiency virus type 1 (HIV-1) as measured by the inability of the virus to replicate in CEM cells. Monocytes, when stimulated, release myeloperoxidase (MPO) and produce H2O2; MPO reacts with H2O2 and chloride to form hypochlorous acid, a known microbicidal agent. The viricidal activity of stimulated monocytes was inhibited by the peroxidase inhibitor azide, implicating MPO, and by catalase but not heated catalase or superoxide dismutase, implicating H2O2. Stimulated monocytes from patients with chronic granulomatous disease (CGD) or hereditary MPO deficiency were not viricidal to HIV-1 unless they were supplemented with the H2O2-generating enzyme glucose oxidase or MPO, respectively. The viricidal activity of stimulated, glucose oxidase-supplemented CGD monocytes and MPO-supplemented MPO-deficient monocytes, like that of normal stimulated monocytes, was inhibited by azide and catalase. Monocytesmaintained in culture differentiate into macrophages with loss of MPO and decreased H2O2 production. The viricidal activity of 3- to 9-day monocyte-derived macrophages was decreased unless MPO was added, whereas the loss of viricidal activity by 12-day-old monocyte-derived macrophages was not reversed by MPO unless the cells were pretreated with gamma-interferon. These findings suggest that stimulated monocytes can be viricidal to HIV-1 through the release of the MPO/H2O2/chloride system and that the decreased viricidal activity on differentiation to macrophages results initially from the loss of MPO and, with more prolonged culture, also from a decreased respiratory burst that can be overcome by gamma-interferon.
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PMID:Viricidal effect of stimulated human mononuclear phagocytes on human immunodeficiency virus type 1. 131 66

Mice infected with LP-BM5 murine leukemia viruses develop a syndrome, termed mouse AIDS (MAIDS), characterized by increasingly severe immunodeficiency and progressive lymphoproliferation. Virus-infected mice were examined for the ability to resist acute infection and to control chronic infection with the protozoan Toxoplasma gondii, a major opportunistic pathogen of individuals infected with human immunodeficiency virus. Mice infected with the retroviruses for 2 or 4 weeks responded normally to challenge with the parasite, but mice inoculated with the protozoan 8 or 12 weeks after viral infection died with acute disease due to T. gondii. Increased sensitivity to acute infection was associated with a reduced ability to produce gamma interferon (IFN-gamma) and with established changes in CD4+ T-cell function. Mice latently infected with T. gondii and then inoculated with the retrovirus mixture were found to reactivate the parasite infection, with 30 to 40% of dually infected animals dying between 5 and 16 weeks after viral infection. Reactivation was associated with reduced proliferation and impaired production of IFN-gamma in response to stimulation with soluble T. gondii antigens or to concanavalin A. Continuing resistance to lethal reactivation in the remaining mice was shown to require CD8+ T cells and expression of IFN-gamma. In addition, it was found that chronic infection with T. gondii altered the course of MAIDS by inhibiting the progression of splenomegaly and immunodeficiency and reducing the expression of both the helper and etiologic defective viruses. These results support previous studies which indicate that infection with T. gondii is controlled by synergistic interactions between CD4+ and CD8+ T cells, the functions of which are progressively impaired during the course of MAIDS.
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PMID:Opportunistic infections and retrovirus-induced immunodeficiency: studies of acute and chronic infections with Toxoplasma gondii in mice infected with LP-BM5 murine leukemia viruses. 132 58

To identify candidate interferons (IFNs) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection and to investigate sequence-function relationships, the antiviral activities of nine species of recombinant IFN-alpha [IFN-alpha A, IFN-alpha B, IFN-alpha C, IFN-alpha D, IFN-alpha J, [Ser116]IFN-alpha J1, IFN-alpha K, IFN-alpha J/C(Fnu4HI), and IFN-alpha A/D(BglII)] were evaluated against HIV-1. MT-2 cells were exposed to various concentrations of each IFN and were then infected with HIV. Protective effect was determined by cell viability using a tetrazolium dye assay. Activity against vesicular stomatitis virus (VSV) was assessed on MDBK and WISH cells. The 50% inhibitory concentration against HIV was 37 +/- 14 pg/ml for IFN-alpha A, and ranged from 15 +/- 3 pg/ml for IFN-alpha J/C(Fnu4HI) to > 90,000 pg/ml for IFN-alpha D. In general, relative activity against HIV was similar to relative activity against VSV on WISH cells. IFN-alpha D was notable for its decreased activity on human cells. The observations suggest that it may be possible to produce IFNs-alpha with more favorable therapeutic indices than currently available IFNs. Furthermore, the anti-HIV activity of IFNs-alpha is not determined solely by their linear amino acid sequence.
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PMID:Anti-HIV-1 activity of recombinant and hybrid species of interferon-alpha. 133 Dec 60

A series of 23 Amaryllidaceae isoquinoline alkaloids and related synthetic analogues were isolated or synthesized and subsequently evaluated in cell culture against the RNA-containing flaviviruses (Japanese encephalitis, yellow fever, and dengue viruses), bunyaviruses (Punta Toro, sandfly fever, and Rift Valley fever viruses), alphavirus (Venezuelan equine encephalomyelitis virus), lentivirus (human immunodeficiency virus-type 1) and the DNA-containing vaccinia virus. Narciclasine [1], lycoricidine [2], pancratistatin [4], 7-deoxypancratistatin [5], and acetates 6-8, isonarciclasine [13a], cis-dihydronarciclasine [14a], trans-dihydronarciclasine [15a], their 7-deoxy analogues 13b-15b, lycorines 16 and 17, and pretazettine [18] exhibited consistent in vitro activity against all three flaviviruses and against the bunyaviruses, Punta Toro and Rift Valley fever virus. Activity against sandfly fever virus was only observed with 7-deoxy analogues. In most cases, however, selectivity of the active compounds was low, with toxicity in uninfected cells (TC50) occurring at concentrations within 10-fold that of the viral inhibitory concentrations (IC50). No activity was observed against human immunodeficiency virus-type 1, Venezuelan equine encephalomyelitis virus, or vaccinia viruses. Pancratistatin [4] and its 7-deoxy analogue 5 were evaluated in two murine Japanese encephalitis mouse models (differing in viral dose challenge, among other factors). In two experiments (low LD50 viral challenge, variant I), prophylactic administration of 4 at 4 and 6 mg/kg/day (2% EtOH/saline, sc, once daily for 7 days, day -1 to +5) increased survival of Japanese-encephalitis-virus-infected mice to 100% and 90%, respectively. In the same model, prophylactic administration of 5 at 40 mg/kg/day in hydroxypropylcellulose (sc, once daily for 7 days, day -1 to +5) increased survival of Japanese-encephalitis-virus-infected mice to 80%. In a second variant (high LD50 viral challenge), administration of 4 at 6 mg/kg/day (ip, twice daily for 9 days, day -1 to +7) resulted in a 50% survival rate. In all cases, there was no survival in the diluent-treated control mice. Thus, 4 and 5 demonstrated activity in mice infected with Japanese encephalitis virus but only at near toxic concentrations. To our knowledge, however, this represents a rare demonstration of chemotherapeutic efficacy (by a substance other than an interferon inducer) in a Japanese-encephalitis-virus-infected mouse model.
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PMID:Antiviral (RNA) activity of selected Amaryllidaceae isoquinoline constituents and synthesis of related substances. 133 40

In an open-label dose-ranging pilot trial, 13 homosexual men with human immunodeficiency virus type 1 (HIV-1) p24 antigenemia after at least 6 weeks of zidovudine monotherapy were continued on zidovudine and given interferon-alpha, 1.25-7.5 x 10(6) units/m2 subcutaneously three times/week. Plasma p24 antigen levels demonstrated a biphasic response, falling initially in 11 patients by a mean of 50% (95% confidence interval, 36%-64%; P = .001) at a median of 11 weeks, but rising steadily thereafter (P = .001). CD4+ cell counts fell by a mean of 7.1 cells/mm3/week (P = .01). Higher initial CD4+ counts predicted greater p24 antigen reductions. At higher interferon doses no greater reductions in p24 antigen occurred, but side effects were more severe and CD4+ lymphocyte counts fell faster. Polymerase chain reaction quantification of HIV-1 DNA in 3 patients showed a biphasic pattern paralleling the p24 antigen response. In sum, although evidence of short-term effects was found, the combination showed no evidence of lasting antiviral activity beyond that achieved with zidovudine alone in patients with advanced HIV-1 infection.
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PMID:Zidovudine-interferon-alpha combination therapy in patients with advanced human immunodeficiency virus type 1 infection: biphasic response of p24 antigen and quantitative polymerase chain reaction. 134 31

The development of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected children with normal T-cell numbers is contrary to previous experience with HIV-infected adults, in whom low CD4+ T-cell numbers predict susceptibility to PCP. To determine whether PCP in HIV-infected children reflects a qualitative T-cell or other immune defect, we studied four HIV-infected children who also had PCP and 10 others without PCP for T-cell and natural killer (NK) cell function. Most of the HIV-infected children had normal T-cell numbers for age, and all had CD4+ T-cell numbers greater than those predictive of PCP in HIV-infected adults. All HIV-infected children had normal T-cell function in vitro. The HIV-infected children as a whole had deficient NK cell cytolysis. We obtained a significant interactive effect of age by health status for NK cell function between patients and age-matched control subjects. All HIV-infected children with defective NK cell function failed to enhance their NK cell cytolysis when their mononuclear cells were stimulated with recombinant interferon alfa (r-IFN-alpha). This NK cell defect in HIV-infected children may facilitate the development of secondary infection.
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PMID:Dysfunction of natural killer cells in human immunodeficiency virus-infected children with or without Pneumocystis carinii pneumonia. 135 23

The 5' ends of all human immunodeficiency virus type I (HIV-1) transcripts have the potential to coordinately regulate translation of HIV-1 mRNAs. Conflicting observations of the translational impact of these sequences in various systems stimulated these analyses of translation in reticulocyte lysates. We report a sensitive, rapid, quantitative, and inexpensive cell-free translation assay in which translational efficiency is monitored by enzymatic assay of the translation products. Using this assay and conventional radiolabeling assays, we demonstrate that the HIV-1 transcript leader inhibits downstream translation and that the stem-loop structure is required. Under our assay conditions, this inhibition occurs predominantly in cis and is not mediated by the 68 kD, interferon-induced, double-stranded RNA-activated kinase (p68). However, under other assay conditions the HIV-1 leader may activate p68 and inhibit translation in trans. We show that variation between individual preparations of cell-free extracts can dramatically alter the magnitude of the translational inhibition by the HIV-1 leader. Further, we provide evidence that a heat-labile factor is required for efficient translation of transcripts containing the HIV-1 leader. These observations provide a foundation for identifying factors required for translation of HIV-1 transcripts.
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PMID:Variable inhibition of cell-free translation by HIV-1 transcript leader sequences. 135 56

Lactoferrin, lysozyme, interferon, and neopterin levels were determined in parotid saliva from 44 individuals with different clinical stages of human immunodeficiency virus (HIV) infection and 19 HIV-seronegative controls. The secretory output of individual components was calculated according to the fluid flow rate. No parotid interferon activity was found in any of the HIV-infected subjects or controls, and no significant differences in parotid lysozyme or neopterin outputs were observed. The lactoferrin output was significantly decreased in HIV-seropositive subjects in parallel with their markedly reduced parotid secretory IgA output. This combined deficiency of parotid lactoferrin and secretory IgA may well contribute to the frequent oral infections seen in subjects with HIV infection.
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PMID:Nonspecific oral immunity in individuals with HIV infection. 137 Nov 57


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