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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular mechanisms underlying the sustained nuclear translocation of NF-kappa B observed in U937 monocytic cells chronically infected with human immunodeficiency virus (HIV) were studied. The activity of the promoter regulating the synthesis of the p105 precursor of the NF-kappa B p50 subunit was enhanced in these cells. Deletions in this promoter indicated that this upregulation was mediated through the NF-kappa B- but not the AP-1-binding motif, by bona fide p50/p65 heterodimers. Analysis of cytosolic extracts indicated that NF-kappa B levels were increased in HIV-infected cells. In contrast to the transient NF-kappa B activation induced by phorbol ester, the permanent NF-kappa B translocation induced by HIV infection was not dependent on PKC isoenzymes alpha and beta as shown by the use of a specific inhibitor (GF 109203X). These observations indicate that during chronic HIV infection of U937 cells, continuous NF-kappa B (p50/p65) translocation results in p105 promoter upregulation with subsequent cytosolic NF-kappa B accumulation, ready for further translocation. This HIV-mediated mechanism results in a self-perpetuating loop of NF-kappa B production.
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PMID:NF-kappa B-dependent induction of the NF-kappa B p50 subunit gene promoter underlies self-perpetuation of human immunodeficiency virus transcription in monocytic cells. 150 2

NF-kappa B, purified from HeLa cell cytosol, and a recombinant p50 subunit of NF-kappa B alone (expressed in and purified from bacteria) both stimulated transcription from the HIV-1 promoter in vitro (at least up to 15-fold). A deletion analysis of the p50 subunit revealed that transcriptional activation was mediated by the conserved c-rel-related domain. I kappa B-beta (or a related protein), which binds to the p65 but not the p50 subunit of NF-kappa B, inhibited stimulation by natural NF-kappa B but not by recombinant p50. Experiments employing a purified transcription system revealed that efficient induction of transcription by both natural NF-kappa B or recombinant p50 required a cofactor fraction in addition to the general initiation factors. Combined with DNA-binding experiments, these studies suggest a role of p50 homodimers in transcriptional activation of certain promoters, with a possible preference for those carrying symmetric NF-kappa B recognition sites, and a potential role of I kappa B-beta in direct transcriptional regulation within the nucleus.
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PMID:Transcriptional regulation of the HIV-1 promoter by NF-kappa B in vitro. 157 71

The nuclear factor (NF)-kappa B transcription factor system is composed of at least four inducible nucleoprotein adducts termed p50, p55 (NF-kappa B p50), p75 (NF-kappa B p65), and p85 (c-Rel). These proteins are expressed in the nuclei of activated T cells in a distinctly biphasic fashion, with p55 and p75 induction occurring within minutes whereas the induction of p50 and p85 occurs after several hours. In contrast, p50 and p55 are constitutively expressed in the nuclei of U937 and THP-1 monocytic cells. However, cellular activation is required for the nuclear expression of p75 in these cells. Additionally, activation of monocytic cells does not result in a significant induction of p85. Tumor necrosis factor alpha induces the nuclear expression of p55 and p75 in these monocytic cells within 20 min, presumably reflecting the liberation of these proteins from I kappa B. In contrast, phorbol myristate acetate (PMA) induces the expression of these proteins with delayed kinetics, raising the possibility that PMA is incapable of mediating the efficient release of p55 and p75 from I kappa B in these cells. These findings highlight important differences in the regulation of these proteins in monocytic cells versus T cells and suggest that the induced expression of NF-kappa B p65 in monocytes may play a central role in the activation of HIV-1 gene expression.
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PMID:Nuclear expression of the 50- and 65-kD Rel-related subunits of nuclear factor-kappa B is differentially regulated in human monocytic cells. 163 4

Biological properties of an AIDS agent first isolated from a native citizen in the USSR are presented. The source of the virus was a young Byelorussian woman who in the near past had had sexual contacts with a citizen from one of the Central Africa countries. The isolate is thought to be of HIV-I type. It replicated perfectly in many continuous lymphocyte lines and had HIV-characteristic morphology. The protein spectrum of the isolate was gp120, gp41, p65/51, p55, p32, p24, p17. Reverse transcriptase activity was detected in the culture fluid of the virus-containing cell cultures. The isolate was designated HIV-IZ.
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PMID:[The biological properties of the HIV isolated from a virus carrier living in the Byelorussian SSR]. 214 58

Studies of NF-kappa B suggest that this enhancer binding activity corresponds to a family of at least four proteins (p50, p55, p75, and p85) differentially induced with biphasic kinetics during T cell activation. While p55 and p50 are closely related to the 50 kd DNA binding subunit of NF-kappa B, p75 and p85 exhibit DNA binding properties that distinguish them from this 50 kd polypeptide and its regulatory subunits I kappa B and p65. All four members of this kappa B-specific protein family are structurally related to the v-Rel oncoprotein and one, p85, appears identical to human c-Rel. v-Rel, but not nontransforming v-Rel mutants, binds to the kappa B enhancer and inhibits NF-kappa B-activated transcription from the IL-2 receptor alpha promoter and HIV-1 LTR. These findings suggest a Rel-related family of kappa B enhancer binding proteins and raise the possibility that the transforming activity of v-Rel is linked to its inhibitory action on cellular genes under NF-kappa B control.
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PMID:The v-rel oncogene encodes a kappa B enhancer binding protein that inhibits NF-kappa B function. 222 78

To investigate a non-RI test which is equivalent to the reverse transcriptase inhibiting antibody test, a reverse transcriptase inhibiting antibody was compared to the absolute number of CD-4 or CD-8 cells or CD-4/-8 ratio and also to photodensitometric analysis for western blotting. There is no correlation of the reverse transcriptase with any test for cell numbers and their ratio. In photodensitometry, relative units of anti-p65 and anti-p51 were compared with reverse transcriptase inhibiting antibody. The reverse transcriptase inhibiting antibody showed a higher correlation to the relative unit of p65 antibodies than that of p51 antibodies. The photodensitometric analysis of western blotting for a serum test may be a possible method to find a prognostic marker in HIV-1 infection.
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PMID:[Comparative evaluation of markers with reverse transcriptase inhibiting antibody in human immunodeficiency virus type 1 infection]. 247 51

Between May 1986 and April 1987 routine screening for anti-HIV antibody was performed by enzyme immunoassay (EIA) on 3344 serum samples. The 1160 samples found positive or borderline were further analysed in Western blot (Wb). We analysed the frequency of different patterns of 'intermediate' Wb reactions (1-3 'specific' bands) and tried to determine their significance by searching for possible modifications of the pattern of reaction a few months later. Of 1160 Wb, 461 were clearly positive, 489 negative and 210 'intermediate'. The latter consisted of: 92 sera with anti-p24 (associated or not), 23 with anti-gp 120 and 160, 16 with anti-p55, 12 with anti-p41, 10 with anti-p65, eight with anti-p17 and four with anti-p31. A non-specific pattern was observed in the remaining 45. Of these sera, 46% were obtained from high risk subjects, 38% from persons without risk and in 16% no reliable information was available. In 30 subjects (24 with p24 and 6 with p41), a second sample was obtained about three months later. The reaction persisted in nine, was replaced by another in five, and disappeared in 15. One subject with anti-p41 in the first sample became clearly positive. In one of the 15 samples with disappearance of the reaction, the antigen p24 was present as the only sign of HIV infection. Later samples of this subject showed clear seroconversion. In many subjects with and without risk of exposure to HIV, the Wb gives an intermediate pattern of reactions (1-3 specific bands), that does not permit definitive conclusion on one single sample. Later controls are therefore necessary. Most of these reactions do not correspond to HIV infection.
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PMID:Serological diagnosis of HIV infection: incidence, outcome and significance of partial reactions found in western blot analysis. 275 92

Cord blood samples were collected from 140 Ugandan neonates after vaginal delivery from healthy women and were tested for the presence of HIV antibodies. Two ELISA tests were used: "HTLV-III EIA" and "ELAVIA". Eleven (7.9%) of the 140 samples were positive and 127 were negative by both ELISA tests. The positivity of 11 samples was confirmed by immunofluorescence assay and Western blot analysis. Two cord blood samples were negative by the "HTLV-III EIA" test but positive by the "ELAVIA" test. These 2 samples were negative by immunofluorescence assay and positive by Western blot analysis. But only antibodies against the proteins p24, p52, and p65 were revealed. Both samples were negative by radioimmunoprecipitation assay for LAV-I and LAV-II antibodies.
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PMID:[HIV-antibodies in cord blood samples from Uganda]. 311 31

Productive infection of T cells with human immunodeficiency virus 1 (HIV-1) typically requires that the T cells be stimulated with antigens or mitogens. This requirement has been attributed to the activation of the transcription factor NF-kappa B, which synergizes with the constitutive transcription factor Sp1 to drive the HIV-1 promoter. Recently, we have found that vigorous replication of HIV-1 takes place in nonactivated memory T cells after syncytium formation with dendritic cells (DCs). These syncytia lack activated cells as determined by an absence of staining for Ki-67 cell cycle antigen. The expression and activity of NF-kappa B and Sp1 were, therefore, analyzed in isolated T cells and DCs from humans and mice. We have used immunolabeling, Western blot analysis, and electrophoretic mobility shift and supershift assays. T cells lack active NF-kappa B but express Sp1 as expected. DCs express high levels of all known NF-kappa B and Rel proteins, with activity residing primarily within RelB, p50, and p65. However, DCs lack Sp1, which may explain the failure of HIV-1 to replicate in purified DCs. Coexpression of NF-kappa B and Sp1 occurs in the heterologous DC-T-cell syncytia that are induced by HIV-1. Therefore, HIV-1-induced cell fusion brings together factors that upregulate virus transcription. Since DCs and memory T cells frequently traffic together in situ, these unusual heterologous syncytia could develop in infected individuals and lead to chronic HIV-1 replication without ostensible immune stimulation.
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PMID:Coexpression of NF-kappa B/Rel and Sp1 transcription factors in human immunodeficiency virus 1-induced, dendritic cell-T-cell syncytia. 747 15

Inflammatory genes are regulated in cells of monocyte (Mo) lineage by a variety of cellular encounters, including adhesion mediated by integrins. The role of the beta 1 family of integrins in the direct induction of immediate early gene expression was analyzed by using the tissue factor (TF) gene. Engagement of alpha 4 or beta 1 on Mo, but not members of the beta 2 integrin family, with specific mAbs as surrogate ligands immediately and directly induced high level surface expression of TF, and accumulation of TF mRNA, as well as production of TNF-alpha and HIV-1 virus. The mechanism responsible for induction of TF gene transcription mediated by the engagement of alpha 4 or beta 1 was elucidated by using THP-1 monoblastic leukemia cells. Functional analysis of plasmids containing the TF promoter expressing the luciferase reporter gene identified a cis-acting integrin-responsive element (InRE), which contained two AP-1 sites as well as a single kappa B-like site. Mutation of either the AP-1 sites or kappa B-like site greatly diminished responsiveness to integrin engagement. This InRE also conferred responsiveness to a heterologous promoter in the same reporter plasmid. Binding of mAbs to either alpha 4 or beta 1 led to nuclear translocation of the c-Rel/p65 heterodimer that preferentially bound to the TF kappa B-like site. In contrast, constitutive binding of AP-1 proteins to the two AP-1 sites was not increased by alpha 4 or beta 1 integrin engagement. These studies expand knowledge of integrin regulation of immediate early gene expression in Mo and molecular encounters that are inferred to play an active role in Mo effector functions.
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PMID:Integrin regulation of an inflammatory effector gene. Direct induction of the tissue factor promoter by engagement of beta 1 or alpha 4 integrin chains. 753 94


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