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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A DNA-binding factor with properties of NF-kappa B and another similar activity are rapidly induced when growth-arrested BALB/c 3T3 cells are stimulated with serum growth factors. Induction of these DNA-binding activities is not inhibited by pretreatment of quiescent cells with the protein synthesis inhibitor cycloheximide. Interestingly, the major NF-kappa B-like activity is not detected in nuclear extracts of proliferating cells, and thus its expression appears to be limited to the G0-to-G1 transition in 3T3 cells. These DNA-binding activities bind many of the expected NF-kappa B target sequences, including elements in the class I major histocompatibility complex and human immunodeficiency virus enhancers, as well as a recently identified NF-kappa B binding site upstream of the c-myc gene. Furthermore, both the class I major histocompatibility complex and c-myc NF-kappa B binding sites confer inducibility on a minimal promoter in 3T3 cells stimulated with serum growth factors. The results demonstrate that NF-kappa B-like activities are immediate-early response proteins in 3T3 cells and suggest a role for these factors in the G0-to-G1 transition.
Mol Cell Biol 1991 Oct
PMID:Induction of NF-kappa B DNA-binding activity during the G0-to-G1 transition in mouse fibroblasts. 192 27

The nucleotide sequences of cDNAs (275 base-pairs) in the non-structural protein 5 regions of Japanese isolates of hepatitis C virus (HCV-J) from the plasma of 11 patients with non-A, non-B hepatitis and the livers of five patients with hepatocellular carcinoma were analyzed. Approximately 14 to 17% of nucleotide sequences of the HCV-Js examined differed from that of the original isolate in the United States (HCV-US). Furthermore, 2.5 to 11% sequence diversity was found among the HCV-Js. The nucleotide sequences of the HCV-Js showed characteristic common differences from that of HCV-US, although they also showed some random substitutions. Plural HCV-J genomes were found in two of the cDNAs derived from liver specimens, and a deletion of 102 nucleotides was found in the cDNA derived from one plasma specimen. These results suggest that HCV-J is a strain different from the HCV-US and that mutation of the viral genome occurs at as high a frequency as in that of the human immunodeficiency virus.
Mol Biol Med 1990 Dec
PMID:Sequence diversity of hepatitis C viral genomes. 196 17

Using thermophilic DNA-polymerase from Thermus thermophilus we have amplified by polymerase chain reaction (PCR) specific DNA sequences of Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). DNA-polymerase from Thermus thermophilus (molecular mass of 80-86 kDa) differs in its physico-chemical properties from DNA-polymerase from Thermus aquaticus (molecular mass of 62-68 kDa). To amplify the specific EBV DNA sequence, oligonucleotide primers for the virus replicon region (oriP region) were used. As a result of amplification, a specific 405-bp DNA fragment was produced.
Mol Cell Probes 1990 Dec
PMID:Amplification of DNA sequences of Epstein-Barr and human immunodeficiency viruses using DNA-polymerase from Thermus thermophilus. 196 9

Thirty eight symptomatic and two asymptomatic patients seropositive for human immunodeficiency virus type-1 (HIV-1) were treated with a natural human interferon alpha (HuIFN alpha). Patients were given 2 IU/kg HuIFN alpha orally once daily in powdered maltose held in the mouth to promote mucosal absorption. This oral immunomodulating HuIFN alpha therapy resulted in an increase in CD4+ lymphocytes, an increase in weight, and a dramatic alleviation of clinical symptoms related to HIV-1 infection.
Mol Biother 1990 Jun
PMID:Low dose oral alpha-interferon therapy for patients seropositive for human immunodeficiency virus type-1 (HIV-1). 197 45

In retroviral proviruses, the poly(A) site is present in both long terminal repeats (LTRs) but used only in the 3' position. One mechanism to account for this selective poly(A) site usage is that LTR U3 sequences, transcribed only from the 3' poly(A) site, are required in the RNA for efficient processing. To test this possibility, mutations were made in the human immunodeficiency virus type 1 (HIV-1) U3 region and the mutated LTRs were inserted into simple and complex transcription units. HIV-1 poly(A) site usage was then quantitated by S1 nuclease analysis following transfection of each construct into human 293 cells. The results showed that U3 sequences confined to the transcription control region were required for efficient usage of the HIV-1 poly(A) site, even when it was placed 1.5 kb from the promoter. Although the roles of U3 in processing and transcription activation were separable, optimal 3' end formation was partly dependent on HIV-1 enhancer and SP1 binding site sequences.
Mol Cell Biol 1991 Mar
PMID:Involvement of long terminal repeat U3 sequences overlapping the transcription control region in human immunodeficiency virus type 1 mRNA 3' end formation. 199 11

In this report we introduce a simple, fast, and reliable method to prepare whole cell or nuclear extracts from small numbers of cells. These extracts were used to study transcriptional activation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in vitro. Our results revealed that the time courses of activation of extracts derived from cells stimulated with the mitogenic lectin phytohemagglutinin (PHA) or with the tumor promoter phorbol 12-myristate 13-acetate (PMA) are different. PMA induces a rapid onset of increased in vitro transcription from the HIV-1 LTR, while PHA causes a slow and sustained response. The biochemical relevance of protein synthesis inhibition by cycloheximide treatment of cells was investigated. In these studies, PMA induction of a change in in vitro transcriptional activity is not dependent on protein synthesis. Cycloheximide alone is insufficient to induce activation. Oligonucleotide-mediated site-directed mutagenesis demonstrated that mutation of the TATA box in the LTR ablated initiation of both basal-level transcription and activation by extracts from cells stimulated with PMA. Surprisingly, mutation of both kappa B sites in the LTR reduced but did not eliminate the in vitro response to extracts prepared at early time points after PHA or PMA stimulation of Jurkat cells. The reduction was greater in extracts derived from cells treated with PMA. Deletion analysis of the HIV-1 LTR revealed at least one region (-464 to -252) capable of suppressing in vitro transcription in extracts from Jurkat cells stimulated by PMA. This result is consistent with early studies of the HIV-1 LTR in transient transfection assays. We therefore have been able to observe distinct regulatory events at early time points after cells are exposed to agents known to induce transcription of both the HIV-1 LTR reporter gene constructs and the HIV-1 provirus itself.
Mol Cell Biol 1991 Apr
PMID:An in vitro transcription analysis of early responses of the human immunodeficiency virus type 1 long terminal repeat to different transcriptional activators. 200 86

The human immunodeficiency virus type 1 (HIV) Rev protein is thought to be involved in the export of unspliced or singly spliced viral mRNAs from the nucleus to the cytoplasm. This function is mediated by a sequence-specific interaction with a cis-acting RNA element, the Rev response element (RRE), present in these intron-containing RNAs. To identify possible host proteins involved in Rev function, we fractionated nuclear cell extracts with a Rev affinity column. A single, tightly associated Rev-binding protein was identified; this protein is the mammalian nucleolar protein B23. The interaction between HIV Rev and B23 is very specific, as it was observed in complex cell extracts. The complex is also very stable toward dissociation by high salt concentrations. Despite the stability of the Rev-B23 protein complex, the addition of RRE, but not control RNA, led to the displacement of B23 and the formation of a specific Rev-RRE complex. The mammalian nucleolar protein B23 or its amphibian counterpart No38 is believed to function as a shuttle receptor for the nuclear import of ribosomal proteins. B23 may also serve as a shuttle for the import of HIV Rev from the cytoplasm into the nucleus or nucleolus to allow further rounds of export of RRE-containing viral RNAs.
Mol Cell Biol 1991 May
PMID:Specific complex of human immunodeficiency virus type 1 rev and nucleolar B23 proteins: dissociation by the Rev response element. 201 66

The production of genetically-engineered, noninfectious virions of human immunodeficiency virus (HIV) represents a novel approach to the development of a safe and effective vaccine for the acquired immune deficiency syndromes (AIDS). Insofar as preparations of inactivated simian immunodeficiency virus (SIV) are now demonstrating protection in immunization-challenge studies in rhesus monkeys, a safe preparation of noninfectious HIV virions produced in a genetically-engineered cell line becomes a logical candidate vaccine for studies in humans. These particles, or pseudovirions, offer distinct advantages over the use of inactivated HIV for human AIDS vaccines. Guarantees of safety without the requirement for inactivation and their potential for structural modification for the modulation of immunogenicity are compelling reasons for the acceptance of HIV pseudovirions as a candidate vaccine in humans.
Mol Immunol 1991 Mar
PMID:Strategy for developing a genetically-engineered whole-virus vaccine against HIV. 201 94

A series of neoglycoproteins was synthesized by coupling of thiophosgene-activated p-aminophenyl derivatives [Biol. Cell. 47:95-110 (1983); J. Histochem. Cytochem. 32:1091-1094 (1984)] of various sugars to human serum albumin. The compounds were evaluated for their in vitro activity against human immunodeficiency virus (HIV). Neoglycoproteins with the highest sugar content were found to be the most potent inhibitors of HIV-1-induced cytopathogenicity. However, this was not due to the nature of the sugar used but, rather, was related to the extra negative charge of the neoglycoproteins. To investigate whether the antiviral activity of the neoglycoproteins exhibited sugar specificity, increased with increasing negative charge, or depended on both sugar specificity and negative charge, we synthesized albumins and neoglycoproteins with an enhanced negative charge, by treatment with formaldehyde or succinic anhydride. Succinylated human serum albumin had the most pronounced net negative charge and had an IC50 of about 1 microgram/ml. No cytotoxicity was observed at concentrations up to 1 mg/ml, implicating a selectivity index (CC50/IC50) of at least 10(3). To elucidate the mechanism of action of these anionic albumins, we investigated whether they interfered with HIV-1 adsorption to the cells, binding of anti-OKT4A monoclonal antibody (mAb) to the CD4 receptor, binding of anti-gp120 mAb to gp120, or inhibition of syncytium formation in co-cultures of HIV-1-infected HUT-78 cells with MOLT-4 cells. From these experiments, we conclude that albumins with an increased negative charge (a) are potent and nontoxic anti-HIV-1 agents, (b) cause a 50% reduction of syncytium formation in the same concentration range as their IC50 in the antiviral assay, and (c) do not bind to the OKT4A epitope of the CD4 receptor and only partly inhibit anti-gp120 mAb-gp120 interaction and virus-cell binding at concentrations that are 100 times higher than their IC50 in the antiviral assay. Therefore, we conclude that the modified albumins interfere with a post-binding event, of which one of the potential mechanisms is an interaction with the gp41 fusion protein, which is necessary for syncytium formation but is not involved in initial virus binding.
Mol Pharmacol 1991 Jun
PMID:Potent in vitro anti-human immunodeficiency virus-1 activity of modified human serum albumins. 205 94

Transfected gene constructs comprising the long terminal repeat (LTR) sequence of the human immunodeficiency virus (HIV) genome spliced to an assayable reporter gene have made possible the evaluation of a lipid mediator, platelet-activating factor (PAF), as a potential HIV transcriptional regulatory molecule. We assessed the activation of the HIV LTR promoter sequence linked to the chloramphenicol acetyltransferase (CAT) reporter gene (HIV-CAT) by PAF in both a human neural (SH-SY5Y neuroblastoma) and a human leukocytic (MOLT-4 T-lymphocyte) cell line. PAF activated expression of the HIV-CAT construct in both the SH-SY5Y and MOLT-4 T-cell lines. PAF-induced CAT activity was approximately six to seven times higher in the SH-SY5Y cells than in the MOLT-4 cells. Preincubation of cells with the specific PAF antagonist BN 52021 completely inhibited CAT expression in both cell lines. The biologically inactive PAF precursor lyso-PAF did not activate CAT expression. Assays for CAT mRNA demonstrated an increase after PAF treatment, an effect that was completely inhibited by BN 52021, and which was not elicited by lyso-PAF. These results show that PAF represents a potential cellular mediator evoking the expression of the HIV genome.
J Mol Neurosci 1990
PMID:Platelet-activating factor activates HIV promoter in transfected SH-SY5Y neuroblastoma cells and MOLT-4 T lymphocytes. 207 79


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