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

We have examined the specificity of human immunodeficiency virus-1 (HIV-1) reverse transcriptase-associated RNase H in removing the tRNA(Lys3) (-)-strand primer in vitro using a model substrate. This substrate represents an intermediate in the reverse transcription process where the tRNA(Lys3) primer has not yet been removed after (+)-strand strong stop DNA synthesis. The substrate consists of an RNA oligonucleotide corresponding to the 3'-terminal 17 nucleotides of the tRNA(Lys3) linked to U5 DNA and annealed to single-stranded DNA containing the U5 and the primer-binding site. Upon incubation with HIV-1 reverse transcriptase p66/p51 heterodimer, the minus-strand DNA product resulting from RNase H cleavage retained the 3'-rA from the model tRNA primer. Changing the 3'-terminal AMP of the model tRNA primer from rA to dA did not alter the RNase H cleavage site. Further, the retention of AMP was not dependent on recognition of adjacent U5 sequences or the CCA terminus of the model tRNA(Lys3). The synthetic RNA primer was released as an intact species by a single endonucleolytic cleavage 5' of the rA. The cleavage patterns of Moloney murine leukemia virus and avian myoblastosis virus RNase H activities on the HIV-1 model substrate were more heterogeneous compared to HIV-1 RNase H. This specificity of HIV-1 RNase H would result in linear DNA molecules with a single rA at the U5 terminus and would provide two bases adjacent to the conserved CA dinucleotide to be cleaved away during the integration process.
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PMID:Specificity of human immunodeficiency virus-1 reverse transcriptase-associated ribonuclease H in removal of the minus-strand primer, tRNA(Lys3). 137 44

Human neural cells are susceptible to infection with human immunodeficiency virus type 1 (HIV-1) in vitro; however, virus replication in these cells is strongly restricted. To understand the mechanism of this restriction, we examined the regulation of HIV-1 expression in glial cell cultures expressing high levels of HIV-1 after transfection of infectious viral DNA and selection. In all cases, high HIV-1 expression declined to low basal levels within 4-8 weeks of cultivation. The decrease in HIV-1 protein production wa paralleled by the decline in the relative levels of the 9.2-, 4.3- and 1.8-kilobase HIV-1 transcripts, but not by significant loss of HIV-1 DNA. Analysis of one long-term cell culture revealed 5 full-length unrearranged HIV-1 DNA copies per cell, but no viral transcripts on Northern blots, and minimal production of infectious virus. HIV-1 replication in these cells was markedly augmented by treatment with sodium butyrate (Na But) and to a lesser extent by 5-azacytidine, dibutyryl AMP and human herpes virus type 6. The virus induced by Na But was infectious. Transient expression assays revealed that Na But was more effective than phorbol myristate acetate in increasing the HIV-1 promoter activity in glial cells. Thus, one phase where glial cells can limit HIV infection is the expression of viral RNA from stable HIV provirus. However, such provirus remains responsive to inductive signals and may be activated to produce infectious HIV.
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PMID:Regulated expression of human immunodeficiency virus type 1 in human glial cells: induction of dormant virus. 138 16

The most important purine nucleotides (NAD, AMP, IMP, GMP, XMP, ADP, ATP, GDP, GTP) were analyzed by HPLC in the lymphocytes of healthy subjects and HIV-1 seropositive patients at different stages of the disease (ARC-AIDS). Several differences, which focus attention on the behaviour of purine nucleotide metabolism in the lymphocytes of these patients, were observed.
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PMID:Analysis of purine nucleotides in lymphocytes from healthy subjects and AIDS patients. 142 Oct 31

A series of nucleotide homo- and heterodimers [3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-di-deoxy-5' adenylic acid (AZT-P-ddA), 3'-azido-3'-deoxythymidilyl-(5',5')-2', 3'-dideoxy;-5'-adenylic acid, 2-cyanoethyl ester [AZT-P(CyE)-ddA], 3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-dideoxy-5'-inosinic acid (AZT-P-ddI), and 3'-azido-3'-deoxythymidilyl-(5',5')-3'-azido-3'-deoxy-5'-thymid ilic acid (AZT-P-AZT)] were synthesized and compared with respect to their anti-HIV and cytotoxic properties to their component monomers in vitro. MT-2 cells were infected with HIV (TM) followed by the addition of drug. The dimers and their respective monomers inhibited HIV-induced syncytia formation, reverse transcriptase production, and the expression of HIV p24 antigen. However, on an equimolar basis, greater anti-HIV potency and enhanced cytotherapeutic indices were observed with the heterodimers when compared with their monomers. Nucleotide dimers, such as AZT-P-ddA, should be actively considered for further evaluation as anti-HIV agents.
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PMID:Nucleotide dimers suppress HIV expression in vitro. 246 62

The present experiments were designed to study whether GTP binding protein activation and the resulting cAMP plays any role in HIV replication. The results showed that cholera toxin (CT) enhanced HIV replication dose dependently in myelo-monocytic cell lines latently infected with HIV-1, U1 and J22HL-60. Three- to 4-fold enhancement of virus production was observed in U1 cells and 4- to 11-fold enhancement in J22HL-60 cells 4 days after treatment with 100 ng/ml of CT. The increment of intracellular cAMP accumulation was parallel with HIV augmentation by CT in both cells. Even at the low concentration 0.1 ng/ml, TNF enhanced virus production to about an 80-fold higher level than the untreated U1 control cells as described previously (11). However, a synergistic effect (80- to 238-fold enhancement) was observed, when TNF-alpha and CT were added together to U1 cells. Similar synergism was seen in J22HL-60 cells. HIV antigen positive cells and gp120 expression were also increased to a similar degree. Phosphodiesterase inhibitor IBMX had no effect on HIV production alone, but potentiated HIV induction by CT and TNF. Adenylate cyclase activator, forskolin (FK), at 100 microM also significantly augmented HIV production (> 4-fold) and potentiated TNF induction in J22HL-60 and U1 cells. On the other hand, CT did not show any effect on HIV replication as well as TNF induction in HIV-1-infected T cell line. Northern blot experiment confirmed that this enhancement was mediated through the activation of HIV transcription. These data suggest that cAMP augments HIV replication and potentiates TNF induction in a particular monocyte-macrophage system.
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PMID:cAMP stimulates human immunodeficiency virus (HIV-1) from latently infected cells of monocyte-macrophage lineage: synergism with TNF-alpha. 768 59

2',5'-Oligoadenylates (2-5A) and derivatives are noncompetitive inhibitors of primer/HIV-1 reverse transcriptase complex formation. The mechanism and specificity of this inhibitory action of 2-5A and 2-5A derivatives have been evaluated with 2-5A molecules modified in ribosyl moiety, chain length, extent of 5'-phosphorylation, and 2',5'-phosphodiester linkage. UV covalent cross-linking of preformed complexes of p66/p66 homodimer or p66/p51 heterodimer recombinant HIV-1 reverse transcriptase and the primer analog pd(T)16 allowed analysis of the initial step in HIV-1 reverse transcriptase-catalyzed DNA synthesis. Utilizing this primer binding assay, it is demonstrated that 2-5A and 2-5A derivatives inhibit the binding of pd(T)16 to HIV-1 reverse transcriptase. This inhibition is specific for the 2',5'-internucleotide linkage in that the corresponding 3',5'-adenylate derivatives do not exhibit inhibitory activity. Enhanced inhibitory properties were observed following modifications of the 2-5A molecule which result in an increase in hydrophobicity. Replacement of the D-ribosyl moiety of 2-5A with the 3'-deoxyribosyl moiety increased the inhibition of primer/HIV-1 reverse transcriptase complex formation 15-20%. 2',5'-Phosphorothioate substitution yielded the most effective inhibitors, with Ki's of 7-13 microM. In all cases, inhibition of primer/HIV-1 reverse transcriptase complex formation showed a preference for the 5'-triphosphate moiety. Nonphosphorylated derivatives were not inhibitory; 5'-monophosphate derivatives exhibited little or no inhibition. The inhibition of primer binding to HIV-1 reverse transcriptase correlated well with the inhibition of DNA-directed DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HIV-1 reverse transcriptase: inhibition by 2',5'-oligoadenylates. 769 66

Retinoids, a group of natural and synthetic vitamin A analogues the receptors of which belong to the superfamily of steroid receptors, can exert profound effects on growth and/or differentiation of embryonic and neoplastic cells. Kaposi's sarcoma (KS), previously a rare multicentric neoplasm, has become epidemic with HIV infection, although the etiology of KS remains obscure. In the present study, the effects of two potent retinoids, all-trans-retinoic acid (RA) and 13-cis-RA, on the expression of retinoic acid receptor alpha and the growth of AIDS-related KS (AIDS-KS) cells were examined. The proliferation of AIDS-KS cells was significantly inhibited by RA and 13-cis-RA in a dose-dependent manner with 50% inhibitory concentration of 1.4 x 10(-10) M and 4.7 x 10(-9) M, respectively, which correlate with their potency. Growth inhibition was time dependent with maximal inhibition of 90% after 3 days of treatment with 10(-8) M RA. Growth inhibition by RA was further potentiated by forskolin (1 microM), an intracellular cyclic AMP-inducing agent. Moreover, RA treatment blocked the proliferative effect of oncostatin M and tumor necrosis factor alpha, two major KS autocrine growth factors. The effects of RA were accompanied by a dramatic increase in nuclear staining for retinoic acid receptor alpha and in the relative number of strongly positive retinoic acid receptor alpha nuclei. Finally, RA induced morphological changes as KS cells became more flattened, better spread, and more adhesive to the substrate. These results suggest that retinoids inhibit proliferation of AIDS-KS cells and further support their utility as therapeutic agents in AIDS-KS.
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PMID:Inhibition of AIDS-Kaposi's sarcoma cell proliferation following retinoic acid receptor activation. 785 Jul 96

T-cell-dependent B cell differentiation involves two phases: an inductive phase of T cell activation followed by an effector phase, which involves stimulation of B cells by activated T cells. We have previously demonstrated that anti-CD3 mAb and antigen-induced T-cell-dependent B cell functions are inhibited by HIV-1 envelope glycoprotein, gp120, at the inductive phase of T-cell-dependent B cell response. In this study we have investigated whether gp120 also inhibits the effector phase of interactions involved in T-cell-dependent-B cell differentiation response. For these studies, CD4+ T cells were first activated with antigen or pokeweed mitogen, cultured with soluble HIV-gp120 or medium for 2 hr, and washed. Coculture of gp120-treated preactivated T cells with autologous B cells resulted in impairment of IgG secretion, but did not affect IgM secretion significantly. The IgG secretion was restored by the addition of PMA (activator of protein kinase C) or forskolin (activator of adenylate cyclase), but not by the addition of ionomycin (inducer of intracellular calcium) to the T plus B cell cultures. A similar pattern of Ig secretion (IgM, no IgG) was observed with B cells of a patient with bare lymphocyte syndrome, indicating a requirement for MHC class II molecule interaction with T cells. These studies suggest that the effector phase of T-B cell interactions are impaired by gp120, and that the mechanism involves a signal transducing event(s), which is dependent upon cyclic AMP and/or protein kinase C. Furthermore, these latter reactions occur subsequent to T-B cell contact-dependent interactions at the effector phase, which involve MHC class II molecules on B cells and CD4 molecules on T cells.
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PMID:Envelope glycoproteins of HIV-1 interfere with T-cell-dependent B cell differentiation: role of CD4-MHC class II interaction in the effector phase of T cell help. 816 44

Adenylosuccinate lyase (ASL) from Bacillus subtilis has been crystallized and structural analysis by X-ray diffraction is in progress. ASL is a 200-kDa homotetramer that catalyzes two distinct steps of de novo purine biosynthesis leading to the formation of AMP and IMP; both steps involve the beta-elimination of fumarate. A single point mutation in the human ASL gene has been linked to mental retardation with autistic features. In addition, ASL plays an important role in the bioprocessing of anti-HIV therapeutics. B subtilis ASL, which shares 30% sequence identity and 70% sequence similarity with human ASL, has been crystallized and data to 3.3 A have been collected at 100 K. The space group is P6(1)22 or P6(5)22 with a = b = 129.4 A; the length of the c-axis varies between 275 and 290 A, depending on the crystal. An analysis of solvent content indicates a dimer in the asymmetric unit, although a self-rotation function and an analysis of native Pattersons failed to identify unambiguously the location of any noncrystallographic symmetry axes. Structure determination by isomorphous replacement is in progress.
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PMID:Crystallization and preliminary structural analysis of Bacillus subtilis adenylosuccinate lyase, an enzyme implicated in infantile autism. 884 70

We have studied the purine nucleotide metabolism in the following cell lines: a), H9 (continuous human T-cell line) and H9/HTLV-III (H9 cell line, infected with RT+ HIV-I virus); b), A3.01 (human lymphoblastoid cell line CD4+) and 8E51 (line A3.01 permanently transfected with RT-HIV-I virus). Purine metabolism was studied by evaluating the content of the most important ribonucleotides (AMP-GMP-IMP-NAD-ADP-GDP-ATP-GTP) and their ratios. We determined several differences between the cell lines before and after viral infection. All nucleotides except triphosphates were reduced in H9/HTLV-III with respect to H9 cells; in 8E51, however, triphosphates were markedly reduced, while monophosphates increased with respect to A3.01 uninfected cells. Also the ratios exhibited different behaviors, for example the total adenine nucleotides total guanine nucleotides ratio (sigma A/sigma G) was enhanced in H9/HTLV-III cells with respect to H9 and unaltered in 8E51 with respect to A3.01 cells. We may conclude that the HIV-I virus strongly influences the purine nucleotide metabolism of the host cells and that the changes are different when induced either by RT+ or RT- virus.
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PMID:Purine ribonucleotide content in infected HIV-RT+ and HIV-RT- lymphoblastoid cell lines. 888 73


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