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)

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

We have developed a vector (pSupexp), for high-level expression of genes, that is dependent on transactivation of the human immunodeficiency virus 1 (HIV-1) long terminal repeat (LTR) by the HIV-1 transactivator protein, Tat. The foreign gene, expressed under transcriptional control of the HIV-1 LTR, and the tat gene, expressed under transcriptional control of SV40 early promoter, are expressed from the same plasmid. The vector also has the neomycin resistance-encoding gene (neo), with G418 being used as a dominant selection marker for stable expression. We have cloned the bacterial cat gene into pSupexp and measured transient CAT production in human HeLa and A549 cells. Our results indicate that pSupexpCAT expresses about 25- to 68-fold higher levels of CAT activity as compared to other standard SV40- and Rous sarcoma virus-based vectors, and three- to fivefold more activity than the cytomegalovirus-based vector. Immunoprecipitation of the CAT protein also revealed a high level of production in human cells.
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PMID:A high-level expression vector for human cells. 139 42

Tuberculosis is responsible for one in four of all avoidable adult deaths in developing countries. Increased frequency and accelerated fatality of the disease among individuals infected with human immunodeficiency virus has raised worldwide concern that control programmes may be inadequate, and the emergence of multidrug-resistant strains of Mycobacterium tuberculosis has resulted in several recent fatal outbreaks in the United States. Isonicotinic acid hydrazide (isoniazid, INH) forms the core of antituberculosis regimens; however, clinical isolates that are resistant to INH show reduced catalase activity and a relative lack of virulence in guinea-pigs. Here we use mycobacterial genetics to study the molecular basis of INH resistance. A single M. tuberculosis gene, katG, encoding both catalase and peroxidase, restored sensitivity to INH in a resistant mutant of Mycobacterium smegmatis, and conferred INH susceptibility in some strains of Escherichia coli. Deletion of katG from the chromosome was associated with INH resistance in two patient isolates of M. tuberculosis.
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PMID:The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. 150 8

We found that serum from individuals with Acquired Immunodeficiency Syndrome (AIDS) had more (p less than .05) catalase activity (31.5 +/- 5.2 U/mL) than serum from healthy control subjects (7.3 +/- 0.8 U/mL). Moreover, serum catalase (but not glutathione peroxidase) activity increased progressively with advancing human immunodeficiency virus (HIV) infection (i.e., AIDS greater than symptomatic infection greater than asymptomatic infection greater than controls). Increases in serum catalase activity correlated with increases in serum hydrogen peroxide (H2O2) scavenging ability and reached levels which decreased exogenous H2O2-mediated injury to cultured endothelial cells without altering neutrophil bactericidal activity or mononuclear cell cytotoxicity in vitro. Serum catalase activity correlated with serum lactate dehydrogenase (LDH) activity but did not appear to be a consequence of erythrocyte (RBC) hemolysis since RBC fragility and serum haptoglobin levels were comparable in HIV-infected and control subjects. Increases in serum catalase activity may reflect and/or compensate for systemic glutathione and other antioxidant deficiencies in HIV-infected individuals.
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PMID:Progressive increases in serum catalase activity in advancing human immunodeficiency virus infection. 151 41

NF-kappa B is a protein complex which functions in concert with the tat-I gene product to stimulate human immunodeficiency virus (HIV) transcription. To determine whether specific members of the NF-kappa B family contribute to this effect, we have examined the abilities of different NF-kappa B subunits to act with Tat-I to stimulate transcription of HIV in Jurkat T-leukemia cells. We have found that the p49(100) DNA binding subunit, together with p65, can act in concert with Tat-I to stimulate the expression of HIV-CAT plasmid. Little effect was observed with 50-kDa forms of p105 NF-kappa B or rel, in combination with p65 or full-length c-rel, which do not stimulate the HIV enhancer in these cells. These findings suggest that the combination of p49(100) and p65 NF-kappa B can act in concert with the tat-I gene product to stimulate the synthesis of HIV RNA.
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PMID:Specific NF-kappa B subunits act in concert with Tat to stimulate human immunodeficiency virus type 1 transcription. 158 34

cis-acting inhibitory region (IR) sequences were identified within the gag/pol gene of the human immunodeficiency virus type 1 (HIV-1) by using a novel feedback-stimulated, rev-independent tat reporter gene to screen HIV-1 sequences in transient expression assays. Two regions, a 1,295-nucleotide segment in the gag gene (IR-1) and a 1,932-nucleotide segment of the pol gene (IR-2), each inhibited reporter gene expression 10- to 20-fold. IR-1 and IR-2 both contained subsequences which inhibited reporter gene expression. Introduction of IR sequences into a heterologous reporter plasmid, pCMV-CAT, resulted in decreased chloramphenicol acetyltransferase expression, suggesting that the inhibitory effect was not restricted to a reporter gene under the control of the HIV-1 promoter. The presence of HIV IR sequences in cis did not alter relative levels of reporter gene RNA; however, fractionation studies revealed IR-containing RNA accumulated in the nucleus. These findings demonstrate that IR sequences within the gag/pol region affect gene expression by altering the cellular distribution of viral RNA.
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PMID:Identification of posttranscriptionally active inhibitory sequences in human immunodeficiency virus type 1 RNA: novel level of gene regulation. 165 66

We have been studying the role of human cytomegalovirus (HCMV) as a potential cofactor in human immunodeficiency virus (HIV)-related disease. The clinical relevance of HCMV is highlighted by the fact that it is a principal viral pathogen in patients with AIDS and is known to infect the same cells as HIV. In this study, we focused on the molecular interactions between HIV and HCMV in human fibroblasts and in the human glioblastoma/astrocytoma-derived cell line U373 MG, cells which can be productively infected by both viruses. Because these cells are CD4-, we used HIV pseudotyped with a murine amphotropic retrovirus as described previously (D. H. Spector, E. Wade, D. A. Wright, V. Koval, C. Clark, D. Jaquish, and S. A. Spector, J. Virol. 64:2298-2308, 1990). Initial studies showed that when cells were preinfected with HIV (Ampho-1B) for 5 days and then superinfected with HCMV, HIV antigen production dropped significantly in the coinfected cells but continued to rise in cells infected with HIV (Ampho-1B) alone. HCMV production, however, was unaffected by the presence of HIV. Further analysis showed that HIV steady-state RNA levels and gag and env protein production were also inhibited in the presence of HCMV. The transcriptional inhibition of HIV was particularly surprising in view of the previous results of several other laboratories as well as our own that HCMV infection stimulates HIV long terminal repeat-chloramphenicol acetyltransferase (LTR-CAT) expression in transient expression assays. To investigate this further, we transfected the HIV LTR-CAT construct into either uninfected cells or cells which had been preinfected with HIV. The cells were infected with HCMV 24 h posttransfection and assayed for CAT gene expression at 48 h after HCMV infection. Although there was some stimulation of the LTR-CAT in cells that were dually infected by HIV and HCMV, it was 16-fold less than that in the cells infected only with HCMV. This suggests that in the presence of the HIV infection, the stimulation of the HIV LTR-CAT gene by HCMV is significantly reduced. Experiments with UV-irradiated HCMV and the HCMV DNA polymerase inhibitor ganciclovir showed that HCMV transcription is necessary for the reduction in HIV production to occur; however, replication of the HCMV genome or any events which take place after DNA replication are not necessary. These results, coupled with the observation that inhibition is usually first seen between 8 and 24 h after HCMV infection, suggest that an HCMV early protein is involved in repression of HIV.
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PMID:Human cytomegalovirus inhibits human immunodeficiency virus replication in cells productively infected by both viruses. 165 86

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

Activity of purine metabolism enzyme, adenosine deaminase (ADA) in lymphocytes and erythrocytes from patients with pneumoconiosis and chronic bronchitis was determined. ADA activity decrease was found in lymphocytes and erythrocytes for both decreases. The observed decrease of ADA activity indicates that after the long term work in mineral dust industry damage of purine metabolism takes place, that is similar to the disturbance observed under secondary immunodeficiency. Changes in activity of superoxide dismutase and catalase show some decrease of functional activity of anti-radical protection. Therefore the results obtained can be used for the selection of a group with highest risk of predisposition to these diseases.
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PMID:[Changes in adenosine deaminase and antioxidative enzyme activity in patients with lung diseases of dust etiology]. 179 56

The adeno-associated virus (AAV) rep gene encodes four proteins (Rep78, Rep68, Rep52, and Rep40) required for AAV DNA replication and AAV gene regulation. In addition, the Rep proteins may have pleiotropic regulatory effects in heterologous systems, and in particular Rep78 may mediate a negative regulatory effect. We analyzed the effects of the AAV rep gene on human immunodeficiency virus type 1 (HIV-1) gene expression. The rep gene proteins of AAV type 2 (AAV2) inhibited the trans-activating ability of HIV-1. Constructs containing the AAV2 rep gene (pHIVrep) or a CAT gene (pBennCAT) expressed from the 5' HIV-1 long terminal repeat were inducible for Rep78 and Rep68 or CAT expression, respectively, when cotransfected with a plasmid containing the HIV-1 tat gene (pARtat). When equivalent amounts of pHIVrep and pBennCAT were cotransfected with increasing amounts of pARtat, expression of CAT activity was decreased. The pHIVrep construct was more inhibitory than plasmids expressing rep from the wild-type AAV2 p5 transcription promoter. rep expression from pHIVrep almost completely inhibited the replication of an HIV-1 proviral clone as measured by reverse transcriptase activity and p24 protein levels. Inhibition of HIV-1 production by Rep protein was also seen at the transcriptional level in that all HIV-1 transcripts were decreased when pHIVrep was present. The inhibitory effects of pHIVrep appear to be mediated primarily by Rep78 and perhaps Rep68. These results suggest that a trans-acting protein from a heterologous virus might be used to inhibit HIV-1 growth.
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PMID:Adeno-associated virus Rep protein inhibits human immunodeficiency virus type 1 production in human cells. 184 99


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