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 herpes simplex virus type 1 (HSV-1)-mediated transactivation of human immunodeficiency virus type 1 (HIV-1) provirus was studied in cell lines containing either integrated tat-defective HIV-1 provirus (HNHIVdt4 cells) or the tat-defective HIV-1 provirus, and a plasmid in which the expression of human alpha 2 interferon (HuIFN-alpha 2) was under the control of the HIV-1 long terminal repeat (LTR) (HNHIV alpha 1 cells). In both cell lines, transcription of the HIV-1 provirus was below the limits of detection, but it could be induced effectively by transfection with a HIV-1 tat-expression plasmid. In HNHIV alpha 1 cells, HuIFN-alpha 2 was induced concomitantly with HIV-1 provirus, although these cells synthesized only low levels of IFN constitutively. In contrast, infections with HSV-1 activated transcription of HIV-1 provirus only in HNHIVdt4 cells but not in HNHIV alpha 1 cells. Similarly in a transient expression assay, HSV-1 up-regulated expression of a HIV LTR-CAT (chloramphenicol acetyltransferase gene) plasmid in HNHIVdt4 but not in HNHIV alpha 1 cells. No major differences could be detected in the expression of HSV-1 immediate-early (IE) genes IE175 and IE110 (which are essential for the activation of HIV-1 LTR) in HNHIVdt4 and HNHIV alpha 1 cells to account for the inability of HSV-1 to induce HIV-1 in HNHIV alpha 1 cells. However, major differences were observed in the binding pattern of NF-kappa B-specific nuclear proteins to the enhancer region of the HIV-1 LTR: whereas binding of the 45-kDa NF-kappa B-specific nuclear protein was detected in nuclear extracts from HNHIVdt4 cells, no protein binding was seen in extracts from HNHIV alpha 1 cells. These results suggest an alternate mechanism by which IFN may alter the expression of cellular and viral genes.
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PMID:Inhibition by interferon of herpes simplex virus type 1-activated transcription of tat-defective provirus. 171 35

The combination of S-dC28 (a phosphorothioate oligodeoxcytidine 28 mer) with AZT, recombinant interferon alpha-A (IFN-alpha A) or dextran sulfate (DS) against replication of human immunodeficiency virus type 1 (HIV-1) were studied in MT4 cells, using both p24 core antigen and reverse transcriptase (RT) assays. Under the standardized conditions, the anti-HIV-1 dose-effect relationships of all test drugs showed sigmoidal curves with the following EC50 values: for the p24 core antigen assay, S-dC28, 0.03 microM; AZT, 0.004 microM; IFN-alpha A, 9.2 U/ml; DS, 0.26 micrograms/ml; for the RT assay, S-dC28, 0.04 microM; AZT, 0.01 microM; IFN-alpha A, 11.6 U/ml; and DS, 0.31 micrograms/ml. A computer software based on the median-effect principle and isobologram techniques were used to quantitatively analyze drug interactions by calculating the combination index (CI) where CI less than 1, = 1, and greater than 1 indicates synergism, additive effect and antagonism, respectively. For p24-ELISA, the interaction of S-dC28 and AZT in combination produced a slight antagonism on HIV-1 replicative inhibition with CI values of 1.29-1.10; for RT assays, at EC50-EC95 levels, the CI values are 1.96-1.11. For p24 core antigen assay, the combination of S-dC28 with IFN-alpha A exhibited a dose-dependent anti-HIV synergism with CI values of 1.15-0.87 at EC75-EC95 levels. The RT assays for the same combination showed a broad synergistic effect with CI values of 0.62-0.60, at EC50-EC95 levels. S-dC28 plus DS showed a nearly additive effect based on both assay methods.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential alteration of the anti-HIV-1 effect of phosphorothioate oligonucleotide S-dC28 by AZT, interferon-alpha, and dextran sulfate. 176 Feb 31

The antiviral activities of various interferon preparations against human immunodeficiency virus (HIV) were evaluated in vitro. Recombinant interferon alpha-A, and beta interferons and leukocyte-derived alpha interferons show similar concentration-dependent antiviral activity. Recombinant and lymphocyte-derived gamma interferons show minimal antiviral activity against HIV replication in normal peripheral blood mononuclear cells, but definite activity against HIV in the H9 lymphocytic and U937 monocyte-macrophage cell lines.
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PMID:Activity of interferons alpha, beta, and gamma against human immunodeficiency virus replication in vitro. 311 63

The current epidemic of acquired immunodeficiency syndrome (AIDS) poses a major threat to our population. Urgently needed are both a vaccine to prevent infection with the etiologic retrovirus, human immunodeficiency virus (HIV), and safe, effective antiviral agents to treat those individuals already infected. The elucidation of viral replicative mechanisms has allowed the development and testing of several agents active against HIV in vitro. Inhibitors of reverse transcriptase that have demonstrated activity include azidothymidine, phosphonoformate, antimoniotungstate (HPA-23), and suramin. Ribavirin and recombinant interferon alpha-A (IFN-alpha-A) also inhibit HIV replication, although their mechanisms of action are less clear. All of these compounds are undergoing early clinical trials in patients with HIV infection. The identification of immunogenic viral proteins may allow the development of one or more subunit vaccines against HIV. Studies are underway to clone appropriate viral genes and incorporate the expressed proteins into vectors for administration. Laboratory models, e.g., chimpanzees, will be inoculated with candidate vaccines and, if successful, this will be followed by clinical trials for safety and efficacy in appropriate human populations seronegative for HIV. Although important problems, such as virus envelope protein variability, need to be addressed, efforts to develop effective vaccines may well prove successful in the years ahead.
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PMID:Prospects for the prevention and therapy of infections with the human immunodeficiency virus. 354 Nov 31

A clinicoimmunological investigation of 1230 patients with chronic nonspecific pulmonary diseases (CNPD) and 380 persons of the control group revealed significant variations in the immune status of patients with bronchopulmonary pathology. Changes in cellular immunity were characterized by a decrease in the number of T-lymphocytes, altered quantitative structure of lymphocyte subpopulations, a decrease in the activity of natural killer cells, leukocyte interferon producing capacity and lymphocyte function revealed by lymphocyte blast-transformation and leukocyte inhibition migration reactions. Changes in humoral immunity were characterized by imbalance of immunoglobulins. Variations in normal indices of local and nonspecific immunity were revealed. Certain relationship between clinical and immunological indices in CNDP patients indicated the presence of immunodeficiency in them confirming the importance of immune mechanisms in the development of chronic bronchopulmonary pathology.
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PMID:[The role of immune mechanisms in the pathogenesis of chronic bronchopulmonary pathology]. 361 36

T cell subsets were analyzed in 33 patients with advanced cancer who were treated with either of two interferon preparations: a partially purified human leukocyte interferon (HulFN-alpha (Le] and a highly purified recombinant interferon (lFLrA). Included in the lFLrA-treated group were eight patients with immunodeficiency and Kaposi's sarcoma. The OKT4+/OKT8+ ratio was used to define the balance between helper/inducer and suppressor/cytotoxic T cell subsets. With both interferon preparations, the mean OKT4+/OKT8+ ratio decreased 24 hours after the first interferon dose. Within the HulFN-alpha (Le) group, the decrease in ratio was related to an increase in OKT8+ cells; in the lFLrA group, it was accompanied by a small decrease in the proportion of OKT4+ cells that was greater than the decrease in OKT8+ cells. Patients treated with lFLrA were followed for the first three weeks of therapy. Most patients treated with lFLrA at all dose levels, ranging from 1 X 10(6) to 54 X 10(6) units per day, had a decrease in OKT4+/OKT8+ ratio on Day 1. No substantial change in the ratio was observed on Days 7, 14, and 22. Patients with immunodeficiency and Kaposi's sarcoma had responses similar to those of patients with other cancers treated with lFLrA. In conclusion, although both HulFN-alpha (Le) and lFLrA induce immediate decreases in the OKT4+/OKT8+ ratio, the T cell subset(s) primarily responsible for the decrease varies with the source of interferon.
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PMID:Analysis of T cell subsets in cancer patients treated with interferon. 619 69

Ovine IFN-tau is a newly described protein related to IFN-alpha that is responsible for maternal recognition of pregnancy in sheep. It has been shown to exhibit potent antiviral and antiproliferative activity. To determine its antiviral activity against feline immunodeficiency virus (FIV) and HIV, the activity of the RNA-dependent DNA polymerase, reverse transcriptase, was assayed in FIV- and HIV-infected feline and human PBL treated with IFN-tau. Significant dose-dependent inhibition of reverse transcriptase activity by IFN-tau was detected by day 6 of culture and was maintained through the peak of virus replication. In addition, production of the FIV core protein, p25, was blocked by IFN-tau. Both the amino- and carboxyl-terminal regions of IFN-tau, as identified by synthetic peptides, appear to be involved in its antiretroviral activity. Comparison of the anti-HIV activities of IFN-tau and recombinant human IFN-alpha2 (rHuIFN-alpha2) indicated that while rHuIFN-alpha2 was toxic to cells at 10,000 U/ml, IFN-tau antiretroviral activity was not associated with a decrease in either cell viability or immunologic reactivity. Thus, IFN-tau displayed potent anti-FIV and anti-HIV activity without the cytotoxicity associated with high concentrations of rHuIFN-alpha2.
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PMID:Potent anti-feline immunodeficiency virus and anti-human immunodeficiency virus effect of IFN-tau. 912 98

The antiviral activity of recombinant feline interferon-gamma (rFeIFN-gamma) against feline immunodeficiency virus (FIV) was investigated. A persistently FIV(Bang)-infected feline T cell line (FeT-J/Bang) was treated with either rFeIFN-omega, rFeIFN-gamma, or recombinant human IFN-alpha2 (rHuIFN-alpha2), and the culture fluids were tested for antiviral activity by reverse transcriptase (RT) assay. FeT-J/Bang cell cultures treated with rFeIFN-omega showed dose-dependent inhibition of RT activity. In contrast, rFeIFN-gamma treatment had no antiviral effect on FIV replication but instead caused a statistically significant enhancement on day 9 of culture. Antiviral activity of rFeIFN-gamma was also tested on feline peripheral blood mononuclear cells (PBMC). PBMC cultures were inoculated with FIV(Bang) and simultaneously treated with either rFeIFN-omega, rFeIFN-gamma, or rHuIFN-alpha2. FeIFN-gamma had no effect on FIV replication, unlike the rFeIFN-omega and rHuIFN-alpha2, which had strong anti-FIV effects. In another study, rFeIFN-gamma treatment was initiated 3 days before FIV(Bang) infection, the day of FIV(Bang) infection, or 3 days post-FIV(Bang) infection and then tested for antiviral activity. The time of initiating rFeIFN-gamma treatment had no effect on the antiviral activity. Hence, these results suggest that unlike rHuIFN-alpha2 and rFeIFN-omega, rFeIFN-gamma has no inhibitory effect on FIV replication in PBMC but causes a slight enhancement in a feline T cell line.
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PMID:Feline immunodeficiency virus lacks sensitivity to the antiviral activity of feline IFN-gamma. 1179 61

Ribavirin in combination with alpha 2 interferon is the consensus treatment for chronic hepatitis C. However, recent preliminary pharmacological studies have suggested that the bioavailability of ribavirin displays great interindividual variability. In order to monitor serum ribavirin levels during combination treatment, we developed and validated a quantitative assay using an approach adaptable for routine hospital laboratories. The method involved solid-phase extraction on phenyl boronic acid cartridges followed by high-performance liquid chromatography with a C(18)-bonded silica column and a mobile phase containing 10 mM ammonium phosphate buffer (with the pH adjusted to 2.5) and UV detection (207 nm). The sensitivity, recovery, linearity of the calibration curve, intra- and interassay accuracies, precision, and stability at 4 degrees C were consistent with its use in the laboratory routine. In addition, other nucleoside analogues sometimes used with ribavirin in patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus did not interfere with the quantification of ribavirin levels. The ribavirin concentration was quantified in 24 serum samples from patients with chronic hepatitis C treated with a combination of ribavirin and alpha 2 interferon. The mean serum ribavirin concentration was 2.67 +/- 1.06 micro g/ml (n = 24) at week 12 of treatment (W12) and 3.24 +/- 1.35 micro g/ml (n = 24) at week 24 of treatment (W24). In addition, ribavirin concentrations displayed high interindividual variabilities: the coefficients of variation of the serum ribavirin concentrations adjusted to the administered dose were 44 and 48% at W12 and W24, respectively. Moreover, the ribavirin concentration was higher in patients with a sustained virological response (n = 11) than in patients with treatment failure (n = 13), with significant intergroup differences at W12 (P = 0.030) and W24 (P = 0.049). The present study describes a simple analytical method for the quantification of ribavirin in human serum that could be a useful tool for the monitoring of ribavirin concentrations in HCV-infected patients in order to improve the efficacy and safety of therapy with ribavirin plus interferon.
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PMID:Ribavirin quantification in combination treatment of chronic hepatitis C. 1249 79

In human immunodeficiency virus type 1 (HIV-1)-infected individuals, virus-induced production of interferon alpha (IFN-alpha) is impaired. In order to obtain regulated expression of IFN-alpha that responds to HIV-1 infection, a recombinant SV40 vector was designed that carries the human IFN-alpha2 cDNA under the control of the HIV-1 long terminal repeat (LTR) (SV[HIVLTR]IFN). Thus, the IFN-alpha2 gene would be trans-activated on infection with HIV-1. This vector was tested to determine if central nervous system (CNS) cell types that may be potential HIV-1 targets could be transduced and protected from HIV. SV[HIVLTR]IFN transduced NT2 cells, a human neuronal precursor cell line, mature neurons derived from NT2 precursor cells, and human primary monocyte-derived macrophages. IFN-alpha2 expression was retained in mature neurons after SV[HIVLTR]IFN-transduced NT2 precursor cells were induced to differentiate using retinoic acid. IFN-alpha expression was detected only after exposing transduced cells to HIV. Furthermore, SV[HIVLTR]IFN-delivered IFN-alpha2 expression significantly inhibited replication of multiple strains of HIV in both NT2 and NT2-derived mature neurons. SV[HIVLTR]IFN transduction also inhibited HIV-1(BaL) replication in human primary monocyte-derived macrophages. Therefore, we have demonstrated the effectiveness of IFN-alpha2, delivered by an SV40 vector driven by HIV-1 LTR as a promoter, to protect several CNS-based, potentially HIV-susceptible cell types. These findings may have implications for therapy of HIV-1 infection in the CNS.
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PMID:Inhibition of HIV-1 in the central nervous system by IFN-alpha2 delivered by an SV40 vector. 1456 57


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