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 chemically modified DNA, apurinic acid (APA), is cytotoxic for human lymphocytes at concentrations above 100 micrograms/ml. At low concentrations (0.05-1 micrograms/ml) APA acts as an inducer interferon gamma (IFN-gamma) in lymphocytes in vitro; the maximum interferon titer of 50 units/ml was reached at 0.4 micrograms/ml. When added to the cells in combination with phytohemagglutinin A (PHA), APA displays a significant synergistic interferon-inducing ability; the maximum titer of 940 units/ml was obtained with 10 micrograms/ml of APA and 6.25 micrograms/ml of PHA. APA also proved to be an effective inhibitor of human immunodeficiency virus (HIV-1) replication in H9 cells. At a concentration of 10 micrograms/ml, APA causes a 49% inhibition of virus growth, while 20 micrograms/ml of APA are required to inhibit expression of HIV-1 p17 and p24 gag proteins by 60%. The mechanism of anti HIV-1 activity of APA likely occurs at the level of viral reverse transcriptase. This enzyme is inhibited by APA in a noncompetitive way with a Ki of 0.39 microM, while the cellular DNA polymerases alpha, beta and gamma are 140- to 300-fold less sensitive to APA.
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PMID:Dual biological activity of apurinic acid on human lymphocytes: induction of interferon-gamma and protection from human immunodeficiency virus infection in vitro. 245 40

The possibility of optimizing the conditions for the cultivation of cells producing human immunodeficiency virus (HIV) was explored. The stimulating effect on the cell cultures of interleukin-2 and specific anti-interferon antibodies was examined. The individual use of interleukin-2 or anti-interferon antibody preparations did not result in any marked enhancement of HIV virus reproduction in the cells, whereas combining of interleukin-2 which stimulated proliferation of T-lymphocytes with poly- and monoclonal anti-interferon antibodies proved to be effective increasing the expression of virus-specific antigens in the cells 1.5-fold. It seems expedient to carry out further screening of different reagents and combinations thereof capable of significantly increasing HIV virus reproduction in cell cultures which would serve as the antigen for diagnostic systems.
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PMID:[Cultivation of cells producing the human immunodeficiency virus]. 245 90

A defect in a trans-regulatory factor which controls major histocompatibility complex class II gene expression is responsible for an inherited form of immunodeficiency with a lack of expression of human leukocyte antigen (HLA) class II antigens. We have recently described and cloned an HLA class II promoter DNA-binding protein, RF-X, present in normal B cells and absent in these class II-deficient regulatory mutants. Here we report that these in vitro results correlate with a specific change in the chromatin structure of the class II promoter: two prominent DNase I-hypersensitive sites were identified in the promoter of the HLA-DRA gene in normal B lymphocytes and found to be absent in the class II-deficient mutant cells. The same two prominent DNase I-hypersensitive sites were observed in normal fibroblastic cells induced by gamma interferon to express class II genes. Interestingly, they were also observed in the uninduced class II-negative fibroblastic cells, which have also been shown to have a normal RF-X binding pattern. We conclude that the two DNase I-hypersensitive sites in the HLA-DRA promoter reflect features in chromatin structure which correlate with the binding of the trans-acting factor RF-X and which are necessary but not sufficient for the expression of class II genes.
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PMID:Inherited immunodeficiency with a defect in a major histocompatibility complex class II promoter-binding protein differs in the chromatin structure of the HLA-DRA gene. 246 88

The production of interferon (IFN) from cultured peripheral blood mononuclear cells (PBMC) after virus or mitogen stimulation was evaluated in 141 patients positive for antibodies to human immunodeficiency virus type 1 (HIV-1). IFN-alpha production by PBMC of patients at Centers for Disease Control (CDC) stage II (Walter Reed [WR] 1) was comparable to that produced by PBMC of healthy controls. However, cells of patients at early CDC stage III (WR 2) produced significantly lower titers of IFN-alpha (P less than .001), and IFN-alpha was almost absent at CDC stage IV (WR 6) (P less than .001). IFN-gamma production was altered in patients at late CDC stage III (WR 4-5) and CDC IV (WR 6). A strong correlation between the disappearance of antibodies to core proteins and low IFN-alpha level was observed. IFN-alpha levels were significantly diminished in patients positive for HIV antigen. Reduced IFN-alpha production paralleled the HIV-1-related depletion of CD4+ lymphocytes and might serve as an additional parameter in defining the stage of HIV-1 infection.
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PMID:Interferon production in patients infected with HIV-1. 246 18

Human immunodeficiency virus (HIV) was readily isolated by co-cultivation of patients' cells with phytohaemagglutinin-stimulated mononuclear cells from umbilical cord blood in 2 ml cultures in 24-well plates. Fluids from cultures of the MLA 144 cell line acted as an excellent source of interleukin-2, and promoted early replication of HIV in the primary cultures. Reverse transcriptase activity was commonly present at significant levels by 4-7 days. In contrast, recombinant IL-2 (recIL-2) did not promote early replication under these conditions. Adequate washing of the phytohaemagglutinin blasts was critical in this system, although others have reported it to be less important under other culture conditions. Cell concentrations and HIV: target cell ratios appeared not to play a major role in early outgrowth of virus. The particular sheep anti-alpha interferon tested resulted in a two-fold reduction in RT activity. Virus was readily transmitted in this simplified cheaper culture system.
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PMID:The value of MLA 144 culture fluid for the isolation of human immunodeficiency virus. 247 86

Sheep and goats develop a chronic, progressive arthritis reminiscent of rheumatoid arthritis, but caused by lentiviruses related to human immunodeficiency virus. The distribution of T lymphocytes in peripheral circulation of two infected sheep with arthritis, one infected sheep with interstitial pneumonia, three asymptomatic sheep, and three uninfected sheep was evaluated. Sheep with clinical disease have depressed ratios of CD4/CD8 lymphocytes in peripheral circulation compared to asymptomatic and uninfected animals. In one sheep, the depressed ratio was due to an absolute increase in CD8-positive lymphocytes. The predominant lymphocyte populations in both synovial fluid and synovium from this animal were also CD8 positive. Macrophages were the other predominant cell population in synovial fluid and were infected with lentivirus. Little cell-free virus was detected in the synovial fluid, although 1 in 400 cells was infected as determined by infectious center assays. Infected cells in the synovial fluid had a reduction in virus gene expression compared to infected cells in peripheral circulation. This reduction in virus gene expression may be due to the presence of interferon-like activity in the synovial fluid.
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PMID:Pathogenesis of ovine lentivirus-induced arthritis: phenotypic evaluation of T lymphocytes in synovial fluid, synovium, and peripheral circulation. 247 38

We have prepared stable cell lines, derived from Vero cells and A3.01 cells, that express a hybrid human alpha 2-interferon gene under control of the human immunodeficiency virus (HIV) long terminal repeat. These cells constitutively produced low levels (50-150 units/ml) of alpha 2-interferon. However, high levels of interferon (10(3) units/ml) could be induced upon trans-activation by the product of the tat gene (pIIIextatIII), and de novo infection by HIV resulted in a moderate increase (400 units/ml) in alpha 2-interferon synthesis. In contrast to the fully permissive HIV replication, in transfected Vero cells or infected A3.01 cells, the transcription and replication of HIV in Vero or A3.01 cells containing the HIV long terminal repeat--alpha 2-interferon hybrid gene (VN89 and A3N89 cells, respectively) was completely inhibited. These data suggest that virus-trans-activated alpha 2-interferon synthesis can be used as a selective inhibitor of HIV replication.
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PMID:Inhibition of human immunodeficiency virus (HIV) replication by HIV-trans-activated alpha 2-interferon. 247 36

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

We evaluated a multicenter cohort of 1219 subjects with hemophilia or related disorders prospectively, focusing on 319 subjects with documented dates of seroconversion to human immunodeficiency virus type 1 (HIV-1). The incidence rate of the acquired immunodeficiency syndrome (AIDS) after seroconversion was 2.67 per 100 person-years and was directly related to age (from 0.83 in persons 1 to 11 years old up to 5.66 in persons 35 to 70 years old; Ptrend = 0.00003). The annual incidence of AIDS ranged from zero during the first year after seroconversion to 7 percent during the eighth year, with eight-year cumulative rates (+/- SE) of 13.3 +/- 5.3 percent for ages 1 to 17, 26.8 +/- 6.4 percent for ages 18 to 34, and 43.7 +/- 16.4 percent for ages 35 to 70. Serial immunologic and virologic markers (total numbers of CD4 lymphocytes, presence of serum interferon or HIV-1 p24 antigen, and low or absent serum levels of anti-p24 or anti-gp120) predicted a high risk for the subsequent development of AIDS. Adults 35 to 70 years old had a higher incidence of low CD4 counts than younger subjects (P less than or equal to 0.005), whereas adolescents had a low rate of anti-p24 loss (P = 0.0007) and subjects 1 to 17 years old had a lower incidence of AIDS after loss of anti-p24 (P = 0.03). These findings not only demonstrate that the risk of AIDS is related directly to age but also suggest that older adults are disproportionately affected during the earlier phases of HIV disease, that adolescents may have a low replication rate of HIV, and that children and adolescents may tolerate severe immunodeficiency better because they have fewer other infections or because of some unmeasured, age-dependent cofactor or immune alteration in the later phase of HIV disease.
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PMID:A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia. 232 15

Cell lines were constructed which permanently express influenza virus-specific RNA. Two approaches were followed. C127 cells were transformed with bovine papilloma virus (BPV) vectors and the resulting cell lines were found to inhibit the replication of influenza virus at low multiplicity of infection (MOI 0.05). However, examination of cellular RNA using single-stranded probes revealed the presence of both (+)sense and antisense RNA transcripts (45-70 copies per cell). In this BPV-based system the inhibitory activity appeared to be associated with a non-specific, interferon (IFN)-mediated effect. In the second approach, an expression system was used which involved 293 cells, a chimeric human cytomegalovirus (CMV)/human immunodeficiency virus (HIV) promoter, and methotrexate- (Mtx)-mediated gene amplification. Cells were found to express up to 7500 copies of influenza virus-specific RNA per cell at a steady state level. In this system no RNA transcripts of the opposite orientation were found. However, all cell lines permanently expressing either (-)sense or (+)sense viral RNA failed to reduce influenza virus titers in a multi-cycle replication experiment (MOI 0.01).
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PMID:Expression of antisense RNA fails to inhibit influenza virus replication. 248 10


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