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kinetics of inhibition of human immunodeficiency virus type 1 (hiv-1) reverse transcriptase by the novel hiv-1-specific nucleoside analogue [2',5'-bis-o-(tert-butyldimethylsilyl)-beta-d-ribofuranosyl]-3'-spiro-5 "- (4"-amino-1",2"-oxathiole-2",2"-dioxide)thymine (tsao-t).[2',5'-bis-o-(tert-butyldimethylsilyl)-beta-d-ribofuranosyl]-3'-spiro- 5"-(4"-amino-1",2"-oxathiole-2", 2"-dioxide)thymine (tsao-t) is a representative of a novel class of nucleoside analogues that are endowed with a potent and specific activity against human immunodeficiency virus (hiv) type 1 and are targeted at the hiv-1 reverse transcriptase (rt). inhibition of hiv-1 rt by tsao-t was reversible and noncompetitive with respect to dgtp as the substrate and poly(c).oligo(dg) as the template/pri ...19921376314
distinction of human immunodeficiency virus type 1 neutralization and infection enhancement by human monoclonal antibodies to glycoprotein 120.there is increasing evidence that sera from hiv-1-infected individuals contain antibodies that enhance infection by hiv-1 in vitro. previous work has demonstrated that complement receptors on t lymphoid cells and fc receptors for igg (fc gamma r) on monocytic cells are required for enhanced infection by antibody-complexed hiv-1. characterization of such infection-enhancing antibodies is essential because immunogenic epitopes which induce enhancing antibodies should be excluded from hiv-1 vaccine ...19921376330
hiv induces il-6 production by human b lymphocytes. role of il-4.in vitro, normal b cells can produce tnf-alpha and il-6 when activated with a first signal, and cytokines and b lymphocytes from some hiv-infected individuals spontaneously secrete tnf-alpha and il-6, although the direct involvement of hiv has not been fully explored. in this study, we examined the effects of hiv (purified virus and a recombinant envelope protein) and various il on tnf-alpha and il-6 in vitro production by highly purified normal b cells. hiv alone did not induce il-6 or tnf-alph ...19921376339
a universal t cell epitope-containing peptide from hepatitis b surface antigen can enhance antibody specific for hiv gp120.peptide-based vaccines that directly target t cell or b cell epitopes may have significant advantages over conventional vaccines. further, synthetic chimeric peptides that combine strong t cell epitopes with poorly immunogenic, but immunodominant, b cell epitopes or strain-conserved b cell epitopes may be useful in eliciting antibody to such important regions. here we characterize a human t cell epitope analyzed in 54 individuals immunized with a hepatitis b virus surface ag vaccine. primary cul ...19921376346
b-cell subsets and platelet counts in hiv-1 seropositive subjects.a subset of b lymphocytes positive for the cd5 antigen have been implicated in several autoimmune disorders. to investigate their role in human immunodeficiency virus type 1 (hiv-1) infection, we studied peripheral-blood b and t lymphocytes from hiv-1-positive patients with (n = 13) and without (n = 18) thrombocytopenia, 8 patients with classic autoimmune thrombocytopenia, and 16 healthy controls. the proportion of cd5-positive b cells was significantly higher in the hiv-1-positive thrombocytope ...19921376384
the clinical application of the interferons: a review. nsw therapeutic assessment group.to review the clinical information on the use of alpha, beta and gamma interferons and to classify the use of alpha interferons in australia according to approved indications, indications for which there is good supporting evidence and indications where therapy is under investigation; and to estimate the cost of therapy with alpha interferons in new south wales in 1991.19921376397
clonal analysis of murine b cell response to the human immunodeficiency virus type 1 (hiv1)-gag p17 and p25 antigens.the antigenicity of hiv-gag p17 and p25 proteins was analyzed using a panel of 52 monoclonal antibodies (mab) derived from 17 independent fusion experiment protocols performed in 12 different laboratories. these mab were tested for their capacity to bind peptides corresponding to sequences of hiv1-bru-gag p17 and p25. thirty-five overlapping peptides (p1 to p35) totally covering the p17 and p25 proteins were used. this study allowed us to identify four immunodominant regions inducing b cell resp ...19921376412
hiv-1 genomic rna diversification following sexual and parenteral virus transmission.human immunodeficiency virus type 1 (hiv-1) genomic rna variation was studied in seven presumed donor-recipient pairs directly following sexual (6/7) or parenteral (1/7) transmission. the first rna-positive serum sample of each recipient and the serum sample of the virus transmitter, identified by epidemiological history and taken within a time bracket of three months of the recipient seroconversion, were analyzed by polymerase chain reaction amplification followed by sequencing of eight cdna cl ...19921376536
immune changes in hiv-1 infection: significant correlations and differences in serum markers and lymphoid phenotypic antigens.human immunodeficiency virus type 1(hiv-1) induces extensive immune cell alterations which can be detected by changes both in serum levels of soluble immune activation products and in several lymphoid phenotypic markers. the current studies were conducted in 70 hiv-1 seropositive subjects to determine whether changes among four important serum immune activation markers (neopterin, beta-2 microglobulin, soluble cd8, and soluble il-2 receptor) and seven lymphoid phenotypic markers (cd38, hla-dr, c ...19921376654
suppressive effect of polyoxometalates on the cytopathogenicity of human immunodeficiency virus type 1 (hiv-1) in vitro and their inhibitory activity against hiv-1 reverse transcriptase.one isopolyoxometalate and 42 heteropolyoxometalates consisting of 3 compounds with the trivacant keggin structure, 2 with the lacunary keggin structure, 30 with the keggin structure, one with the wells-dawson structure and 6 with miscellaneous structures were tested for their suppressive effect on the cytopathogenicity of human immunodeficiency virus type 1 (hiv-1) in vitro and inhibitory activity against hiv-1 reverse transcriptase. in contrast to the leading interpretations which attribute th ...19921377101
new human gene encoding a positive modulator of hiv tat-mediated transactivation.the human immunodeficiency virus-1 (hiv-1) protein tat is a potent activator of virus gene expression. tat functions through a sequence known as tar, located immediately downstream of the transcription start site in the long terminal repeat. several observations suggest that cellular factors cooperate with tat in the overall transactivating process. we have isolated a human complementary dna from the new gene mss1, which may encode such a cellular factor, by transcomplementation of a yeast sgv1- ...19921377363
treatment of human immunodeficiency virus associated with oral aphthous ulcers with inhaled steroids. 19921377372
angiogenesis--the interdisciplinary challenge. 19921377528
a possible role for cysteine residues in the fidelity of dna synthesis exhibited by the reverse transcriptases of human immunodeficiency viruses type 1 and type 2.hiv reverse transcriptases (rts) have few cysteine residues relative to other rts and retain their dna polymerization functions following chemical modification by thiol-specific reagents. the functional role of the cysteines in the fidelity of the dna-dependent dna synthesis of hiv rts has been addressed by chemical modification of the wild-type enzymes in combination with the analysis of an enzymatically active mutant hiv-1 rt in which all cysteines were modified to serines. we have observed an ...19921377646
one-year follow-up on the safety and efficacy of isoprinosine for human immunodeficiency virus infection. scandinavian isoprinosine study group.the safety and clinical impact of isoprinosine in hiv-infected individuals were assessed in a multicentre, randomized, double-blind, 24-week study phase, followed by an optional 24-week open treatment phase. the results of the double-blind phase have been reported. of 866 hiv-seropositive patients randomized, 832 subjects were eligible for efficacy analysis. on completion of the double-blind phase, 596 patients started open treatment. all patients were evaluated with regard to progression to aid ...19921377741
preferential interaction of human immunodeficiency virus reverse transcriptase with two regions of primer trna(lys) as evidenced by footprinting studies and inhibition with synthetic oligoribonucleotides.primer trna regions involved in the interactions between human immunodeficiency virus reverse transcriptase (hiv rt) and trna(lys) were studied by digestion of primer with pancreatic ribonuclease in the presence or absence of hiv rt. the acceptor stem of trna(lys) is not noticeably protected against nuclease action in the presence of hiv rt, while this enzyme clearly protects part of the anticodon and dihydrouridine loops of trna(lys). the acceptor stem of primer trna was digested by rnase a onl ...19921377751
[hepatitis serology: use and interpretation].presently five viruses causing hepatitis are known, the hepatitis viruses a (hav), b (hbv), c (hcv), d (hdv) and e (hev). the genomic structure is known of most of all these viruses as well as some of their structural and regulatory gene products. using radio- and enzyme immunoassays viral antigens can be detected for hbv and hdv as well as specific antibodies against all the five viruses. the results of these tests are the basis for the diagnosis and the follow-up of these infections but differ ...19921377839
antiretroviral therapy: strategies beyond single-agent reverse transcriptase inhibition. 19921377897
antibodies of hiv-1 positive subjects and experimentally immunized primates and rodents bind to sequence divergent regions of the third variable domain (v3) of gp120.several motifs have been found to be the target of the neutralizing antibody response to hiv, the human immunodeficiency virus. one of the well characterized motifs maps to a loop within the third hypervariable region (v3) of the exterior envelope glycoprotein gp120 at amino acid positions 308-331 and is referred to as the principal neutralizing determinant (pnd). the sequence of this v3 loop raises the question of the immunogenicity and the degree of diversity of the antibody response to the pn ...19921377948
human monoclonal and polyclonal anti-human immunodeficiency virus-1 antibodies share a common clonotypic specificity.human monoclonal and purified polyclonal anti-human immunodeficiency virus (hiv)-1 antibodies were tested for binding to a murine monoclonal anti-idiotypic antibody (1f7, igm, kappa). four human monoclonal anti-p24 and three human monoclonal anti-gp120 antibodies express the 1f7 clonotype, while one human monoclonal anti-gp41 antibody does not bind to 1f7. affinity-purified anti-p24 and anti-gp120 antibodies from hiv-1-infected individuals also react with 1f7. western blot analysis and enzyme-li ...19921378015
parameters that influence processive synthesis and site-specific termination by human immunodeficiency virus reverse transcriptase on rna and dna templates.we have examined the parameters that determine the length and distribution of products synthesized processively by the human immunodeficiency virus reverse transcriptase (hiv-rt). on native or homopolymer templates, the overall length distribution of processively synthesized products is increased by increased temperature or deoxynucleoside triphosphate concentration, or decreased ionic strength. specific terminations of processive synthesis on either native dna or rna templates occur most freque ...19921378301
functional analysis of primers and templates in the synthesis of dna catalyzed by human immunodeficiency virus type 1 reverse transcriptase.the kinetics of copying of poly(a).(dt)n, poly(a).(u)n, poly(da).(dt)n and poly(a).(dt)9-u by reverse transcriptase of human immunodeficiency virus-1 (hiv-1) has been studied and the binding affinity of the enzyme, for template or primer, determined. short oligonucleotides and dttp served as primers in the hiv-1 reverse-transcriptase-dependent dna synthesis. km and vmax were measured as functions of the primer chain length; the logarithm of the values of both km and vmax increased linearly up to ...19921378404
the effects of cysteine mutations on the catalytic activities of the reverse transcriptase of human immunodeficiency virus type-1.the reverse transcriptase (rt) of the human immunodeficiency virus type 1 (hiv-1) has only 2 cysteine residues at positions 38 and 280. in order to investigate the role of these cysteines in the structure and function of the enzyme, we have previously modified each of the cysteines to serines employing site-directed mutagenesis. two of the mutant forms of hiv-1 rt, the single mutant of cysteine 280 and a double mutant with both cysteines modified, were purified. in the present study we have comp ...19921378433
purification and characterization of heterodimeric human immunodeficiency virus type 1 (hiv-1) reverse transcriptase produced by in vitro processing of p66 with recombinant hiv-1 protease.active recombinant reverse transcriptase (rt) of human immunodeficiency virus type 1 (hiv-1) with an amino-terminal extension containing a hexa-histidine sequence has been prepared in milligram quantities in a pure heterodimeric (p66/p51) form by coordinated applications of immobilized metal affinity chromatography (imac) and hiv-1 protease treatment. the precursor protein, isolated from extracts of recombinant escherichia coli by imac in a predominantly unprocessed form (p66), migrated on sodiu ...19921378437
differential inhibitory effects of tibo derivatives on different strains of simian immunodeficiency virus.recently, several classes of compounds have been shown to be extremely selective inhibitors of human immunodeficiency virus type 1 (hiv-1) replication in vitro. these include the tetrahydro-imidazo[4,5,1-jk][1,4]-benzodiazepin-2(1h)-one and -thione (tibo), 1-(2-hydroxyethoxymethyl)-6-(phenylthio)-thymine (hept), dipyridodiazepinone, pyridinone and bis(heteroaryl)piperazine derivatives. the hallmark of these new antiviral compounds is a specific interaction with reverse transcriptase (rt) of hiv- ...19921378481
a monoclonal antibody to cd4 domain 2 blocks soluble cd4-induced conformational changes in the envelope glycoproteins of human immunodeficiency virus type 1 (hiv-1) and hiv-1 infection of cd4+ cells.the murine monoclonal antibody (mab) 5a8, which is reactive with domain 2 of cd4, blocks human immunodeficiency virus type 1 (hiv-1) infection and syncytium formation of cd4+ cells (l. c. burkly, d. olson, r. shapiro, g. winkler, j. j. rosa, d. w. thomas, c. williams, and p. chisholm, j. immunol., in press). here we show that, in contrast to the cd4 domain 1 mab 6h10, 5a8 and its fab fragment do not block soluble cd4 (scd4) binding to virions, whereas they do inhibit scd4-induced exposure of cry ...19921378510
galactosyl ceramide (or a closely related molecule) is the receptor for human immunodeficiency virus type 1 on human colon epithelial ht29 cells.the gastrointestinal tract is considered to be a major route of infection for human immunodeficiency virus (hiv). infection of human colon epithelial cells by hiv is not blocked by anti-cd4 antibodies known to block infection of lymphoid cells (j. fantini, n. yahi, and j. c. chermann, proc. natl. acad. sci. usa 88:9297-9301, 1991), suggesting the presence of an alternate receptor for hiv on these cells. in this report, we show that (i) a monoclonal antibody specifically directed against galactos ...19921378511
partial reverse transcripts in virions from human immunodeficiency and murine leukemia viruses.reverse transcription of the retroviral genome is thought to start after virions enter target cells. purified preparations of human immunodeficiency virus were found to contain virus-specific dna, detectable by polymerase chain reaction amplification. this dna resulted from reverse transcription in newly assembled virus particles and not from contamination by cellular dna, because virions contained a striking excess of early versus late transcripts and because the accumulation of these products ...19921378513
viral dna carried by human immunodeficiency virus type 1 virions.a fundamental step in the replication of retroviruses is the reverse transcription of the viral rna genome into a double-stranded dna provirus. retroviruses are believed to carry genomic information only as rna, and synthesis of dna is thought to start only after virus entry into the infected cell. we report here that infectious mature human immunodeficiency virus type 1 virions contain viral dna of heterogeneous size. this heterogeneity seems to result from random stops of reverse transcription ...19921378514
progression of early steps of human immunodeficiency virus type 1 replication in the presence of an inhibitor of viral protease.we have evaluated a possible role for human immunodeficiency virus type 1 protease during early steps of replication. for these studies, a specific inhibitor of human immunodeficiency virus protease, ro31-8959, was used. synthesis of viral cdna, its integration into cellular dna, and its transcription were determined during a one-step, acute infection of mt-4 cells. no consistent difference in any of these parameters was noted between control-infected cultures and those treated with protease inh ...19921378515
inhibition of human immunodeficiency virus activity by phosphorodithioate oligodeoxycytidine.phosphorothioate oligodeoxynucleotides exert a sequence-independent cytoprotective effect against human immunodeficiency virus type 1 (hiv-1). we now report that phosphorodithioate-containing oligodeoxycytidines are very potent inhibitors of hiv-1 reverse transcriptase in vitro, as they exhibit an increasing inhibitory effect with length and number of phosphorodithioate internucleotide linkages. this inhibitory effect can be at least 30-fold greater with phosphorodithioate oligodeoxycytidine tha ...19921378623
cd14 is involved in control of human immunodeficiency virus type 1 expression in latently infected cells by lipopolysaccharide.lipopolysaccharide (lps) potently stimulates human immunodeficiency virus type 1 (hiv-1) long terminal repeat-directed transcription in transfected monocyte-macrophage cell lines and dramatically increases hiv-1 production in the latently infected monocyte-macrophage-like cell line u1. this response to lps, however, can only be observed after pretreatment of the u1 cells with granulocyte-macrophage colony-stimulating factor (gm-csf). cd14, the differentiation antigen that acts as a receptor for ...19921378624
inhibition of human immunodeficiency virus type 1 reverse transcriptase by 3'-blocked oligonucleotide primers.human immunodeficiency virus type 1 (hiv-1) reverse transcriptase (rt) (ec 2.7.7.49) with a high specific activity has been purified from the overexpressing escherichia coli strain dh5 alpha [pjs3.7]. steady-state kinetics of dna synthesis catalysed by rt were analysed on polyriboadenylate 20-mer of (3'-5')deoxythymidylate [poly(ra).(dt)20] and polyribouridylate 20-mer of (3'-5')-deoxyadenylate [poly(ru).(da)20] homopolymeric template-primers. km values of 40 and 140 nm (3'-oh ends) and kcat val ...19921378738
fidelity of the reverse transcriptase of human immunodeficiency virus type 2.the relatively low fidelity of human immunodeficiency virus type 1 reverse transcriptase (hiv-1 rt) was implicated as a major factor that contributes to the genetic variability of the virus. extension of mismatched 3' termini of the primer dna was shown to be a major determinant of the infidelity of hiv-1 rt. human immunodeficiency virus type 2 (hiv-2) also shows extensive genetic variations. therefore, we have analyzed the fidelity of the dna-dependent dna polymerase activity of hiv-2 rt and co ...19921378791
structure-function relationships of hiv-1 reverse transcriptase determined using monoclonal antibodies.the reverse transcriptase (rt) of human immunodeficiency virus type 1 (hiv-1) is one of the main targets in approaches to the chemotherapy of aids. a detailed knowledge of structure-function relationships of this enzyme is a prerequisite for rational drug design. we have used monoclonal antibodies as tools to identify functionally important regions of the protein. the preparation of 23 murine monoclonal antibodies (mab) against hiv-1 reverse transcriptase and their different effects on the enzym ...19921378837
specificity of human immunodeficiency virus-1 reverse transcriptase-associated ribonuclease h in removal of the minus-strand primer, trna(lys3).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 d ...19921378844
evaluation of viral-lysate enzyme-linked immunosorbent assay kits for detecting human immunodeficiency virus (type 1) infections using human sera standardized by quantitative western blotting.the first generation of proprietary reagents for detecting antibodies to the human immunodeficiency virus type 1 (hiv-1) by enzyme-linked immunosorbent assay (elisa) used as antigen partially purified virus from cell culture lysates. these tests, which are still in use, may vary in their antibody measurement capabilities if different proportions of the viral polypeptides are present in the viral lysate mixtures. we determined the quantities of antibodies in the serum of persons infected with hiv ...19921378850
a new electron microscope positive staining method for viruses in suspension.a new procedure for the positive staining of viruses in suspension, the tokuyasu staining procedure (tsp), was evaluated using a non-enveloped virus, rotavirus; an enveloped virus, rubella virus and two glutaraldehyde-treated enveloped viruses, human t cell lymphotropic virus type i (htlv-i) and human immunodeficiency virus type 1 (hiv-1) as models. the tsp involves an initial staining of the virus with uranyl acetate (ua) followed by thin embedding in a mixture of ua and polyvinyl alcohol (pva) ...19921378851
murine monoclonal antibodies directed against the transmembrane protein gp41 of human immunodeficiency virus type 1 enhance its infectivity.monoclonal antibodies (mabs) were raised against the transmembrane protein (tm) gp41 of human immunodeficiency virus type 1 (hiv-1, strain htlv-iiib). the reactivity of three tm-specific mabs was investigated in several tests, elisa, immunostaining of western blots, immunofluorescence and an alkaline phosphatase-anti-alkaline phosphatase assay. epitope mapping was done by using overlapping gp41 peptides produced as escherichia coli fusion proteins and synthetic peptides. in an in vitro assay, al ...19921378882
de novo reverse transcription is a crucial event in cell-to-cell transmission of human immunodeficiency virus.the proposal that replication of human immunodeficiency virus type 1 (hiv-1), mediated by cell-to-cell transmission of the virus, might bypass de novo reverse transcription was tested by using one-step cell-to-cell and cell-free virus infection systems. two well characterized reverse transcriptase (rt) inhibitors, azidothymidine at 20 microm and phosphonoformic acid at 100 micrograms/ml, blocked hiv replication completely following both cell-free virus and cell-to-cell transmission infection, as ...19921378883
immunotherapy for superficial bladder cancer. a developmental and clinical overview.superficial bladder cancer is one of the few solid human malignancies in which immunotherapy has been proved to be effective. bacillus calmette-guérin was the vaccine which opened the door for this innovative approach. in an era of remarkable achievements in biotechnology, it is truly amazing that this throwback to the stone age of tumor immunology has not yet been replaced by a more (or equally) effective substitute. potential candidates are already on the horizon and deserve a comprehensive ev ...19921378982
human moabs produced from normal, hiv-1-negative donors and specific for glycoprotein gp120 of the hiv-1 envelope.human moabs of igm class were developed against three regions of the hiv-1 envelope. uninfected donor lymphocytes were immunized in vitro with recombinant protein pb1. four out of five antibodies were directed to different parts of the v3 region, which contains a major neutralizing site. two out of these antibodies were directed to more than one amino acid sequence, indicating reactivity to discontinuous sites. two of the human moabs inhibited viral spread between cells in tissue culture, interp ...19921379134
biochemical studies on the reverse transcriptase and rnase h activities from human immunodeficiency virus strains resistant to 3'-azido-3'-deoxythymidine.a series of biochemical investigations to compare the dna polymerase and rnase h functions of the reverse transcriptases (rts) corresponding to azidothymidine (azt)-sensitive and -resistant human immunodeficiency virus (hiv) strains are described. steady-state kinetic studies with purified recombinant enzymes utilizing several templates and three inhibitors, 3' azido-3' deoxythymidine triphosphate (azttp), 3-amino-thymidine 5'-triphosphate, and 2',3'-didehydro-2',3'-dideoxythymidine 5'-triphosph ...19921379238
interaction of trna(lys-3) with multiple forms of human immunodeficiency virus reverse transcriptase.the interaction of several forms (p51, p66, and p66/p51) of recombinant human immunodeficiency virus type 1 reverse transcriptase (hiv-1 rt) with a synthetic derivative of its cognate replication primer, trna(lys-3), has been determined by gel-mobility shift analysis. while p66/p51 rt is proficient in trna binding, preparations of p66 and p51 display only weak binding at elevated protein:trna ratios, despite the former containing both rna-dependent dna polymerase and ribonuclease h (rnase h) act ...19921379242
inactivation of the human immunodeficiency virus type 1 (hiv-1) by ultraviolet and x irradiation.here we report the kinetics of inactivation of hiv-1 by ultraviolet (uv) or x irradiation. inactivation of hiv-1 by uv irradiation followed quasi first-order, i.e., single-hit, kinetics. the ld37 for inactivation of syncytia formation in supt1 cells by limiting dilutions was approximately 780 j/m2. the ld37 for inactivation of hiv-1-induced syncytia by uv irradiation was nearly identical when measured in uv repair-proficient and -deficient lymphoblastoid cell lines (lcls), demonstrating that imm ...19921379369
inhibition of heat inactivation of reverse transcriptase of human immunodeficiency virus type 1 by seropositive sera.the reverse transcriptase (rt) activity of a lysate of human immunodeficiency virus type 1 (hiv) was almost completely inactivated by incubation at 56 degrees c for 20-30 min. the heat-inactivation of rt in the virus lysate or purified rt was partially inhibited in the presence of some human sera or plasma containing antibodies against hiv. the igg fraction purified from the seropositive sera was responsible for stabilization of rt upon heat inactivation. this is a new assay system for detection ...19921379577
unequal human immunodeficiency virus type 1 reverse transcriptase error rates with rna and dna templates.sequence variation in the type 1 human immunodeficiency virus (hiv-1) results, in part, from inaccurate replication by reverse transcriptase. although this enzyme is error-prone during synthesis in vitro with dna templates, the fidelity of rna-dependent dna synthesis relevant to minus-strand replication in the virus life cycle has not been examined extensively. in the present study, we have developed a system to determine the fidelity of transcription and reverse transcription and have used it t ...19921379727
rna pseudoknots that inhibit human immunodeficiency virus type 1 reverse transcriptase.high-affinity ligands of the reverse transcriptase of human immunodeficiency virus type 1 (hiv-1) were isolated by the selex procedure (systematic evolution of ligands by exponential enrichment) from rna populations randomized at 32 positions. analysis of these ligands revealed a pseudoknot consensus with primary sequence bias at some positions. we demonstrated that at least one of the ligands inhibits cdna synthesis by hiv reverse transcriptase but fails to inhibit other reverse transcriptases. ...19921379730
alterations in tumor angiogenesis associated with stable expression of the hiv tat gene.recent evidence suggests that the human immunodeficiency virus type 1 (hiv) trans-activator gene (tat) has transforming properties and may be a causative factor in the development of certain types of cancers, in particular kaposi's sarcoma (i.e., vogel j. et al. nature 335:606-611, 1988). to help elucidate the potential role or roles of the hiv tat gene in neoplastic transformation, cell lines were constructed that constitutively express a functional tat gene product. hela cells were coelectropo ...19921379815
effects of bone marrow stimulatory cytokines on human immunodeficiency virus replication and the antiviral activity of dideoxynucleosides in cultures of monocyte/macrophages.cells of the monocyte lineage are important targets for the replication of human immunodeficiency virus (hiv). our group and others have previously shown that granulocyte-macrophage colony-stimulating factor (gm-csf) stimulates hiv replication in monocyte/macrophages, but that it also enhances the anti-hiv activity of 2',3'-dideoxy-3'-azidothymidine (azt). in the present study, we have explored the effects of other bone marrow stimulatory cytokines on the replication of hiv and on the anti-hiv a ...19921379854
didanosine. a review of its antiviral activity, pharmacokinetic properties and therapeutic potential in human immunodeficiency virus infection.didanosine is a dideoxynucleoside analogue which undergoes intracellular conversion to the putative active triphosphate metabolite. the active metabolite appears to inhibit viral reverse transcriptase and terminate the proviral dna, and produces virustatic inhibition of actively replicating human immunodeficiency virus (hiv) at clinically relevant concentrations. in phase i studies didanosine had beneficial effects on various surrogate markers of clinical efficacy and also improved clinical mani ...19921379914
immunization with soluble protein-pulsed spleen cells induces class i-restricted cytotoxic t lymphocytes that recognize immunodominant epitopic peptides from plasmodium falciparum and hiv-1.ctl lines specific for two different proteins derived from the human pathogens, plasmodium falciparum (malaria) circumsporozoite protein and hiv-1 reverse transcriptase, were obtained by immunizing mice with protein-pulsed syngeneic spleen cells. the lysis of the target cells was dependent on a class i mhc molecule and the accessory molecule cd8. immunodominant epitopic peptides were identified previously in the two proteins using murine ctl derived after immunization with recombinant virus or s ...19921380039
examination of sera from human immunodeficiency virus type 1 (hiv-1)-infected individuals for antibodies reactive with peptides corresponding to the principal neutralizing determinant of hiv-1 gp120 and for in vitro neutralizing activity.sera from human immunodeficiency virus type 1 (hiv-1)-infected individuals from the united states and tanzania were examined for antibody reactivity to four synthetic peptides which corresponded to the principal neutralizing determinant from the v3 region of hiv-1 gp120. we observed that the majority of sera from both countries contained antibodies reactive with a v3 peptide whose sequence is based on that of the hiv-1 mn isolate. we were unable to establish a relationship between the presence o ...19921380094
persistence of azidothymidine-resistant human immunodeficiency virus type 1 rna genotypes in posttreatment sera.the rate of reversion from azidothymidine (zidovudine; azt) resistance was studied by direct sequencing of human immunodeficiency virus type 1 (hiv-1) virion rna in sera from four patients who discontinued long-term treatment. before cessation of treatment, all four patients harbored hiv-1 with multiple mutations reported to confer azt resistance. in three patients, slow reversions of these mutations starting after 9, 9, and 18 months were detected. the slow reversions indicate that azt-resistan ...19921380098
discontinuous, conserved neutralization epitopes overlapping the cd4-binding region of human immunodeficiency virus type 1 gp120 envelope glycoprotein.monoclonal antibodies have been isolated from human immunodeficiency virus type 1 (hiv-1)-infected patients that recognize discontinuous epitopes on the gp120 envelope glycoprotein, that block gp120 interaction with the cd4 receptor, and that neutralize a variety of hiv-1 isolates. using a panel of hiv-1 gp120 mutants, we identified amino acids important for precipitation of the gp120 glycoprotein by three different monoclonal antibodies with these properties. these amino acids are located withi ...19921380099
detection of a human intracisternal retroviral particle associated with cd4+ t-cell deficiency.a number of non-human-immunodeficiency-virus (hiv) type 1 disorders are associated with cd4+ t-cell deficiency and dysfunction. however, the etiopathogenesis of cd4+ t-cell immunodeficiency in these disease states remains unclear. human intracisternal retroviral (hicrv) particles were detected in a lymphoblastoid cell line exposed to mononuclear cells from a patient with severe cd4+ t-cell deficiency without risk factors for hiv infection. ultrastructurally, the hicrv is distinct from hiv-1, hiv ...19921380169
(-)-2'-deoxy-3'-thiacytidine is a potent, highly selective inhibitor of human immunodeficiency virus type 1 and type 2 replication in vitro.the (-)-enantiomer of 2'-deoxy-3'-thiacytidine (3tc) was found to be a potent and selective inhibitor of human immunodeficiency virus types 1 (hiv-1) and 2 (hiv-2) in vitro. we determined its antiviral activity against a number of laboratory strains of hiv-1 and hiv-2 in a range of cd4-bearing lymphocyte cell lines (mean 50% inhibitory concentration [ic50] range, 4 nm to 0.67 microm). 3tc was also active against a range of hiv-1 strains in peripheral blood lymphocytes (mean ic50 range, 2.5 to 90 ...19921380229
characterization of a mouse/human chimeric monoclonal antibody (c beta 1) to a principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein.a chimeric mouse-human antibody (c beta 1) was constructed that recognized the principal neutralizing domain (pnd) of human immunodeficiency virus type 1 (hiv-1) gp120. the constant (c) immunoglobulin regions (c gamma 1 and c kappa) of a mouse monoclonal antibody, 0.5 beta, were substituted for the human c gamma 1 and c kappa by recombining the dna modules encoding variable or c regions. the dna constructs were then transfected into x63 ag8.653 myeloma cells. a clone with a high production of th ...19921380258
delineation of immunoreactive, conserved regions in the external glycoprotein of the human immunodeficiency virus type 1.immunization of mice and rats with purified external glycoprotein gp120 from two divergent human immunodeficiency virus type 1 (hiv-1) isolates resulted in the development of seven hybridomas secreting monoclonal antibodies able to recognize regions of gp120 which are common among divergent strains of hiv-1. these monoclonal antibodies cross-reacted with env glycoproteins from one african (rutz), one haitian (rf), and three north american viral isolates, namely iiib, mn, and 451 by either immuno ...19921380259
study of viral replication in hiv-1-infected cem t-cell subclones which are reduced in their ability to form syncytia.the derivation of ethyl-methanesulfonate (ems) mutagenized subclones from the cem t-cell line has been described. these clones expressed cd4 and bound soluble gp120, however, two of the generated clones were markedly reduced in their ability to form syncytia after infection with either gp160-vaccinia vector or cell-free human immunodeficiency virus type 1 (hiv-1). here, we asked at what stage(s) viral infection is blocked in these cells. polymerase chain reaction (pcr) analysis revealed that at ...19921380260
inhibition of hiv infection by a novel cd4 domain 2-specific monoclonal antibody. dissecting the basis for its inhibitory effect on hiv-induced cell fusion.hiv use the cd4 molecule as their primary cellular receptor. residues in the n-terminal domain (d1) of cd4 are crucial to hiv attachment through the gp120 envelope component. however, other regions of cd4 appear to be required subsequently for virus- and cell-cell fusion. little is understood of the post-binding steps which may differ between hiv variants. we report a novel anti-cd4 mab that does not block cd4/gp120 binding, but that does efficiently block both viral infection and cell-cell sync ...19921380539
hematopoietic growth factors in aids.three hematopoietic growth factors, erythropoietin, gm-csf, and g-csf, have all been evaluated in the context of hiv infection. recombinant human epo is currently licensed for therapy of anemia related to zidovudine and is well tolerated in this patient population. although myelosuppression can clearly be overcome using recombinant human gm-csf or g-csf in hiv-infected hosts, the clinical benefits for such patients are still not determined. it is likely that these growth factor therapies will al ...19921380730
l-696,229 specifically inhibits human immunodeficiency virus type 1 reverse transcriptase and possesses antiviral activity in vitro.l-696,229 (3-[2-(benzoxazol-2-yl)ethyl]-5-ethyl-6-methyl-pyridin-2 (1h)-one) is a specific inhibitor of human immunodeficiency virus type 1 (hiv-1) reverse transcriptase (rt) activity that possesses antiviral activity in cell culture (w.s. saari, j.m. hoffman, j.s. wai, t.e. fisher, c.s. rooney, a.m. smith, c.m. thomas, m. e. goldman, j. a. o'brien, j. h. nunberg, j. c. quintero, w. a. schleif, e. a. emini, and p. s. anderson, j. med. chem. 34:2922-2925, 1991). in the present study, the rt-inhib ...19921380788
identification of the human immunodeficiency virus reverse transcriptase residues that contribute to the activity of diverse nonnucleoside inhibitors.the reverse transcriptase (rt) of human immunodeficiency virus type 1 (hiv-1) is potently inhibited by a structurally diverse group of nonnucleoside compounds. these include pyridinone derivatives, tetrahydroimadazo[4,5,1-j,k][1,4]-benzodiazepin-2(1h)-one and -thione, and bi-rg-587 (nevirapine). the compounds act noncompetitively, by an unknown mechanism, with respect to template-primer and nucleotide substrates. despite a high degree of similarity between the hiv-1 and hiv-2 rts, the hiv-2 enzy ...19921380789
active site studies of human immunodeficiency virus reverse transcriptase.the active site of human immunodeficiency virus reverse transcriptase (hiv1-rt) was probed using three group-specific reagents: phenylglyoxal (pg), n-ethylmaleimide (nem), and pyridoxal 5'-phosphate (plp). the inactivation of hiv1-rt by arginine-specific pg was found to be completely protected against by adding primer-template. the potential active site arginine was localized to position 277 in the primary structure, suggesting that the polymerase domain of the enzyme should be considered as ext ...19921380826
[repertoire of epitopes of human immunodeficiency virus proteins and the search for vaccines and diagnostic kits]. 19921380907
class ii (i-ad) restricted t-cell recognition of the v3 loop region of hiv-1 gp120.a cd4+ and gp120-specific t-cell line, and subclone, were established from balb/c mice following immunization with recombinant gp120, using an adjuvant formulation (alum) acceptable for use in the human. the recognition specificity was determined against a panel of synthetic peptides corresponding to the primary sequence of the hxb2 strain of human immunodeficiency virus (hiv). an epitope was identified, corresponding to amino acid residues 322-341, and a further series of truncated peptides est ...19921381202
recombinant glycoprotein 120 of human immunodeficiency virus is a potent interferon inducer.cells infected with human immunodeficiency virus (hiv) induce antiviral activity in peripheral blood mononuclear cells (pbmc) from healthy donors. this activity is neutralized by anti-interferon-alpha antibody and partially destroyed at ph 2. previous studies with enriched cell populations and monoclonal antibodies suggest that b lymphocytes are the main ifn-producing cells, and that both cd4 and hla class ii antigens are essential for ifn induction. since the initial event of hiv infection of c ...19921381203
pyridoxal-5'-phosphate inhibits the polymerase activity of a recombinant rnaase h-deficient mutant of hiv-1 reverse transcriptase.we have investigated the ability of pyridoxal-5'-phosphate to inhibit a recombinant deletion mutant of human immunodeficiency virus type 1(hiv-1) reverse transcriptase (rt) which is missing the last 23 amino acids of the c-terminus. this mutant reverse transcriptase is characterized by normal polymerase activity as compared with full-length enzyme; however, it has no rnase h activity. inhibition studies with pyridoxal-5'-phosphate showed several differences as compared with inhibition of full-le ...19921381204
inhibition of the reverse transcriptase activity and replication of human immunodeficiency virus type 1 by as 101 in vitro.in a search for compounds active against human immunodeficiency virus type 1 (hiv-1), it was found that the novel low-molecular weight immunoenhancer ammonium trichloro(dioxyethylene-o,o'-) tellurate (as101) suppresses production of hiv-1 in vitro. treatment of hiv-1-infected peripheral blood mononuclear cells (pbmc) with increasing concentrations of as101 resulted in substantial inhibition of virus production as measured by both reverse transcriptase (rt) activity and antigen presence in supern ...19921381205
dehydroepiandrosterone (dhea) and synthetic dhea analogs are modest inhibitors of hiv-1 iiib replication.down-regulation of epstein-barr virus (ebv) induced transformation of human lymphocytes in vitro by dehydroepiandrosterone (dhea), a naturally occurring human steroid secreted by the adrenal gland has been demonstrated. this article reports on the effects of dhea and its novel synthetic analogs 16 alpha-fluoro-5-androsten-17-one (8354) and 3 beta-hydroxy-16 alpha-fluoro-5 alpha-androstan-17-one (oh8356) on human immunodeficiency virus (hiv-1) replication. treatment with dhea, 8354, or oh8356 res ...19921381206
studies on a type d retrovirus isolated from an aids patient lymphoma.the development of aids-related lymphomas (arl) has been on the rise in recent years. during an analysis of arl from aids patients, one individual developed atypical syncytial variants of high-grade burkitt's-type b-cell lymphomas, which prompted further study. however, the search for a hiv-1 retrovirus, which we hypothesized was infecting these cells, led to the subsequent discovery of a type d retrovirus in two early-passage lymphoma cell lines derived from this patient. nucleotide and amino a ...19921381207
cytotoxic t lymphocyte responses in the peripheral blood of children born to human immunodeficiency virus-1-infected mothers.cytotoxic t lymphocytes (ctl) are present at high activities in adult patients infected with the human immunodeficiency virus (hiv). in this report, ctl effectors were identified in peripheral blood mononuclear cells (pbmc) of children born to hiv-1-infected mothers. these ctl killed hla-matched hiv-1-infected h9 target cells or doubly transfected p815-a2-env, gag or nef mouse tumor cells, which expressed the viral antigens in association with hla-a1/a3 or hla-a2, respectively. hiv-1-specific ct ...19921381309
functional analysis of hiv-1 reverse transcriptase amino acids involved in resistance to multiple nonnucleoside inhibitors.several novel, structurally distinct classes of specific human immunodeficiency virus type 1 (hiv-1) reverse transcriptase (rt) nonnucleoside inhibitors have been described recently. these include the pyridinone derivatives l-697,639, l-697,661, and l-696,229 as well as bi-rg-587 and the tetrahydroimidazo[4,5,1-j,k]-benzodiazepin-2(1h)-one and -thione compounds. previous studies have implicated involvement of the rt amino acid residues at positions 103, 181, and 188 in the activity of the compou ...19921381350
characterization of hiv isolates arising after prolonged zidovudine therapy.human immunodeficiency virus type 1 (hiv-1) was isolated from five patients with late-stage disease treated with zidovudine (zdv) for more than 1 year. peripheral blood mononuclear cells (pbmcs) were used for all virus isolations and to assay for drug resistance. the isolates exhibited a 10- to 100-fold decrease in zdv susceptibility compared to pretreatment isolates. multiple clones of a 618 bp segment of the hiv reverse transcriptase gene encompassing codons 60-250 were sequenced for each isol ...19921381438
inhibition of human immunodeficiency virus and growth of infected t cells by the immunosuppressive drugs cyclosporin a and fk 506.the effects of the immunosuppressive drugs cyclosporin a and fk 506 were studied on cells chronically infected with human immunodeficiency virus type 1 (hiv-1) as well as on uninfected and newly infected cells. when cells chronically infected with hiv-1 or with hiv-2 were cocultivated with uninfected cells in the presence of cyclosporin a or fk 506 there was a delay in the formation of syncytia and of cytopathic effects. this inhibitory effect was not due to decreased membrane expression of cd4. ...19921381509
human and murine monoclonal antibodies directed against a conserved sequence from gp41 (aa583-599) of human immunodeficiency virus type 1.human spleen cells from an hiv-seropositive donor were immunized in vitro with the aa583-599 peptide conjugated to an heptalysyl core. this sequence was derived from the putatively hiv-immunosuppressive region of hiv1 gp41. the same conjugated peptide was used to immunize mice. one human and one mouse igm monoclonal antibody (mab) directed against the aa583-599 peptide were obtained. the two mab had distinct patterns of reactivity against a panel of 42 peptides with modified sequences. neither o ...19921381515
human immunodeficiency virus replication: modulation by cellular levels of camp.hiv infection is associated with qualitative and functional immune deficiencies. it has been shown that the in vitro infection of cd4+ cells with hiv was associated with sustained elevation of camp and cgmp. in the present report the role of camp on hiv replication in mt-4 cells was investigated. the mt-4 cells were infected with hiv (strain 3b), in the presence or absence of agents that increase intracellular levels of camp, through different mechanisms. at selected times postinfection, hiv rep ...19921381600
lymphadenopathy and hepatosplenomegaly in the 1st year in children infected by hiv-1 in zaire.the children of 50 women positive for antibody to human immunodeficiency virus type 1 (hiv-1) and 42 children of antibody-negative mothers were examined for lymphadenopathy and hepatosplenomegaly at 3-month intervals during the 1st year of life. lymphadenopathy was found to be significantly more frequent at 6 months (p less than 0.01), 9 months (p less than 0.001) and 12 months (p less than 0.01) in children who were subsequently shown to be infected with hiv-1. hepatomegaly was seen more freque ...19921381891
seropositivity to hepatitis c virus (hcv) in saudi children with chronic renal failure maintained on haemodialysis.twenty saudi children (mean age: 7.7 years) with chronic renal failure who had received several blood transfusions were screened for antibodies to hepatitis c virus (anti-hcv), antibodies to the human immunodeficiency virus (anti-hiv) and antibodies to the various markers of hepatitis b virus (hbv). prevalence of anti-hcv antibodies was significantly higher in these patients (45%) than in controls (1%) (p less than 0.001). in contrast, the exposure rate to hbv was similar in both groups (15.0% i ...19921381899
immunogenicity of recombinant core particles of hepatitis b virus containing epitopes of human immunodeficiency virus 1 core antigen.a gag protein segment of human immunodeficiency virus 1 (hiv-1) has been fused to a c terminally truncated core antigen of hepatitis b virus (hbcag) using an e. coli expression system. fusion of 90 amino acids of hiv-1 gag protein to hbcag still allowed the formation of capsids presenting on their surface epitopes of hiv-1 core protein, whereas fusion of 317, 189, or 100 amino acids of gag prevented self-assembly of chimeric particles. mice immunized with recombinant particles emulsified with fr ...19921381912
conformational changes of hiv reverse transcriptase subunits on formation of the heterodimer: correlation with kcat and km.the reverse transcriptase (rt) from the human immunodeficiency virus (hiv) is initially expressed as a 66-kda protein and is subsequently proteolytically processed in vivo to form a 66-kda/51-kda heterodimer. comparison of circular dichroism spectra of the 66-kda, 51-kda, and heterodimeric forms of rt indicates that the conversion is accompanied by dramatic changes in subunit conformation. the mean residue ellipticity per subunit at 220 nm decreases from -10.7 x 10(3) deg cm2 dmol-1 for the 66-k ...19921381960
cross-sectional survey of hiv infection among patients with tuberculosis in nairobi, kenya.evidence from many countries suggests an association of human immunodeficiency virus (hiv) infection and tuberculosis of major public health significance. in order to begin assessing the impact of hiv on tuberculosis in kenya, we have determined the hiv-1 seroprevalence among tuberculosis patients and compared the clinical characteristics of tuberculosis in hiv-positive and hiv-negative patients in two cross-sectional studies at the infectious disease hospital (idh) and the ngaira avenue chest c ...19921381970
synthesis and anti-human immunodeficiency virus type 1 (hiv-1) activity of 3-substituted derivatives of 3'-azido-3'-deoxythymidine (azt), and inhibition of hiv-1 reverse transcriptase by their 5'-triphosphates.various 3-substituted 3'-azido-3'-deoxythymidine analogs (2a-i) were prepared by the reaction of 3'-azido-3'-deoxythymidine (1), azt with n,n-dimethylformamide dialkylacetal or alkyl bromide in the presence of base and their activities against human-immunodeficiency virus type-1 (hiv-1) were evaluated. the corresponding 5'-triphosphate analogs (9) were also synthesized in order to examine inhibition of hiv-1 reverse transcriptase activity. beyond expectation, some n3-derivatives of azt were foun ...19921381996
effect of human chorionic gonadotropin (hcg) on reverse transcriptase activity in hiv-1 infected lymphocytes and monocytes.the majority of infants born to hiv-positive mothers are not infected in utero, suggesting that the pregnancy factors produced by fetal trophoblasts may provide protection against hiv-1 infection. except for steroid female hormones, little is known of other pregnancy factors that may regulate either resistance or susceptibility to hiv-1. human chorionic gonadotropin (hcg)--the major glycoprotein produced by the placental trophoblast throughout the pregnancy--was tested on reverse transcriptase a ...19921382034
functional analysis of novel selective mutants of the reverse transcriptase of human immunodeficiency virus type 1.we have generated by site-directed mutagenesis plasmids that induce the synthesis of specific mutants of the reverse transcriptase (rt) of human immunodeficiency virus type 1 (hiv-1). these recombinant mutants of hiv-1 rt, designed on the basis of our previous studies of hiv-1 and hiv-2 rts, were analyzed for structure-function relationship by assessing their rna-dependent and dna-dependent dna polymerase as well as the ribonuclease h activities. three groups of mutants were studied. 1) we have ...19921382052
interaction of trnalys with the p66/p66 form of hiv-1 reverse transcriptase stimulates dna polymerase and ribonuclease h activities.the precursor homodimeric p66/p66 form of human immunodeficiency virus type-1 reverse transcriptase (hiv-1 rt) possesses the dna polymerase and rnase h activities involved in the synthesis of the double-stranded provirus dna. reverse transcription is initiated from trnalys in the case of hiv-1. the present study confirmed that interactions between hiv-1 rt and trnalys induce protein conformational changes and demonstrated that these interactions stimulate the enzymatic activities associated with ...19921382072
evidence for a human immunodeficiency virus type 1-mediated suppression of uninfected hematopoietic (cd34+) cells in aids patients.hematopoietic progenitor (cd34+) cells were purified from the bone marrow of 6 human immunodeficiency virus (hiv) type 1-seropositive cytopenic patients and 10 healthy donors. hiv-1-seropositive patients showed a reduced number of granulocyte/macrophage, erythroid, and megakaryocyte progenitors and also a progressive and significant decline of numbers of cd34+ cells in liquid culture, which did not result from a productive or latent hiv-1 infection of cd34+ cells. however, all hiv-1-seropositive ...19921382106
worldwide prevalence of lentivirus infection in wild feline species: epidemiologic and phylogenetic aspects.the natural occurrence of lentiviruses closely related to feline immunodeficiency virus (fiv) in nondomestic felid species is shown here to be worldwide. cross-reactive antibodies to fiv were common in several free-ranging populations of large cats, including east african lions and cheetahs of the serengeti ecosystem and in puma (also called cougar or mountain lion) populations throughout north america. infectious puma lentivirus (plv) was isolated from several florida panthers, a severely endan ...19921382145
subtyping of human immunodeficiency virus isolates with a panel of monoclonal antibodies: identification of conserved and divergent epitopes on p17 and p25 core proteins.we have investigated the feasibility and significance of subtyping of human immunodeficiency virus (hiv) isolates with monoclonal antibodies (mab) raised against the core proteins of hiv. a panel of 37 mab tested for reactivity with hiv1 oligopeptides was used to analyse the antigenic relatedness among 14 hiv isolates which included 12 isolates of hiv1 from different geographical origins and 2 isolates of hiv2. three out of these 37 mab reacted with conserved epitopes expressed by all 14 hiv iso ...19921382219
distinctive pattern of infection and replication of hiv1 strains in blood-derived macrophages.the macrophage-tropic virus hiv1-par, isolated from cerebrospinal fluid of hiv1-seropositive man, induced cytopathic effect accompanied by different magnitude of the virus production in blood-derived macrophages (bdm) obtained from different donors. hiv1-par-specific rna was detected by in situ hybridization in 15 and 66% of bdm producing low and high levels of virus, respectively. in contrast with hiv1-par, infection of bdm with two laboratory strains adapted to t-cell lines, hiv1-lav prototype ...19921382338
amino acid residues of the human immunodeficiency virus type i gp120 critical for the binding of rat and human neutralizing antibodies that block the gp120-scd4 interaction.we have characterized the discontinuous epitopes recognized by two rat and three human neutralizing monoclonal antibodies (mab) by examining the effect of single amino acid changes in conserved residues of gp120 on mab recognition. a human mab derived from an infected individual, 448d, and two rat mabs, 39.13g and 39.3b, respectively, derived by immunization with native recombinant gp120, recognize similar epitopes. recognition of the envelope glycoproteins by these mabs was affected by changes ...19921382339
prevention of the spread of hiv-1 infection with nonnucleoside reverse transcriptase inhibitors.certain bisheteroarylpiperazines (bhaps) directly inhibit the replication of human immunodeficiency virus type 1 (hiv-1) and block the spread of infection to susceptible populations of cells. at a 1 microm concentration three analogs, u-87201, u-88204, and u-89674, inhibited the replication of hiv-1 in mt-2 cells by 83, 100, and 93%, respectively. at the same concentration, u-88204 completely inhibited replication of primary hiv-1 isolates in peripheral blood mononuclear cells. replication of 3' ...19921382341
analysis of the backbone dynamics of the ribonuclease h domain of the human immunodeficiency virus reverse transcriptase using 15n relaxation measurements.the backbone dynamics of the uniformly 15n-labeled ribonuclease h (rnase h) domain of human immunodeficiency virus (hiv-1) reverse transcriptase have been investigated using two-dimensional inverse-detected heteronuclear 15n-1hnmr spectroscopy. 15n t1, t2, and nuclear overhauser enhancement (noe) data were obtained for 107 out of a total of 134 backbone amide groups. the overall rotational correlation time (tau r) for the protein at 26 degrees c is 10.4 ns. the backbone n-h vectors for all the m ...19921382587
fidelity of the rna-dependent dna synthesis exhibited by the reverse transcriptases of human immunodeficiency virus types 1 and 2 and of murine leukemia virus: mispair extension frequencies.human immunodeficiency viruses type 1 and 2 (hiv-1 and hiv-2, respectively) exhibit extensive genetic variations. it was postulated that much of this genetic variability stems from the low fidelity of the reverse transcription step. both hiv reverse transcriptases (rts) were shown to be particularly error-prone during the in vitro dna-dependent dna synthesis relative to other retroviral rts. extension of mismatched 3'-termini of the primer dna was shown to be a major determinant in the infidelit ...19921382590
phosphorylation of carbovir enantiomers by cellular enzymes determines the stereoselectivity of antiviral activity.two enantiomers of carbovir, a carbocyclic analog of 2',3'-dideoxyguanosine, were compared with respect to their phosphorylation and the phosphorylation of their nucleotides by mammalian enzymes. 5'-nucleotidase catalyzed the phosphorylation of (-)-carbovir, which is active against hiv (human immunodeficiency virus), but did not phosphorylate (+)-carbovir. (-)-carbovir monophosphate was 7,000 times more efficient as a substrate for gmp kinase than was (+)-carbovir monophosphate. pyruvate kinase, ...19921383219
quantitation of antigen-specific immune responses in human immunodeficiency virus (hiv)-infected individuals by limiting dilution analysis.the lymphocyte proliferative response to recall antigens is lost following hiv infection. we sought to devise a means by which the functional immune status of persons in the early stages of hiv infection could be monitored quantitatively. the response to tetanus toxoid was examined in 45 hiv-infected individuals and 11 controls using conventional lymphocyte proliferative assays concurrently with limiting dilution analysis utilizing the secretion of interleukin-2 as the measure of a response. our ...19921383258
detection of a vigorous hiv-1-specific cytotoxic t lymphocyte response in cerebrospinal fluid from infected persons with aids dementia complex.aids dementia complex is a common neurologic disorder in later stages of hiv-1 infection. because virus-specific ctl have been shown to contribute to neurologic disease in certain viral illnesses, we examined the cerebrospinal fluid of hiv-1-infected persons with various stages of aids dementia complex for the presence of hiv-1-specific ctl. in five of six subjects studied, hiv-1-specific ctl were identified in the cerebrospinal fluid. these ctl were directed at epitopes within the gag, reverse ...19921383338
idiotypic expression of anti-gp120 antibodies in unrelated human immunodeficiency virus-infected individuals.although it is recognized that human immunodeficiency virus (hiv) env genes exhibit a high degree of variability, little is known about the molecular heterogeneity of gp120-specific antibodies in infected individuals. as a first step to approach this issue, we investigated the idiotypic relatedness of anti-gp120 antibodies present in the serum of hiv-infected individuals. idiotypic determinants (idiotopes) are fingerprints of the variable region of the antibody molecule and, as such, they repres ...19921383396
identification of a gag protein epitope conserved among all four groups of primate immunodeficiency viruses by using monoclonal antibodies.five monoclonal antibodies (mabs) were raised against the gag proteins of simian immunodeficiency virus (siv) from african green monkey (sivagmtyo-7). two mabs reacted with the matrix protein p17 and the other three with the core protein p24. studies on the cross-reactivity of the mabs revealed that the anti-p24 mabs detected an epitope shared by the viruses belonging to the human immunodeficiency virus type 2 (hiv-2)/sivmac group and sivagmtyo-7 and sivagmtyo-5. the anti-p17 mabs recognized an ...19921383399
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