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

We have used the human myelomonocytic cell line HL-60 as a model system to determine whether human immunodeficiency virus type 1 (HIV-1) infection affects differentiation of myeloid progenitor cells. HL-60 cells were infected with three HIV-1 isolates (IIIB, NL4-3 and PM213). HIV-1 antigen expression and cytopathicity in HL-60 cells infected with each of the three isolates was delayed by approximately 15 days as compared to those in the prototypic T cell line, H9. Chronically infected HL-60 cells and clonal lines derived from them were treated with dimethyl formamide (DMF) and induced to differentiate into granulocytes. Approximately the same percentage of these cells as of DMF-treated, uninfected HL-60 cells differentiated. Superoxide production by infected and uninfected DMF-induced cells was similar. Likewise, approximately the same percentage of cells in infected and uninfected cultures became adherent and were positive for non-specific esterase when monocytic differentiation was induced. The data demonstrate that HL-60 cells infected with HIV-1 are capable of morphological and functional granulocytic and monocytic differentiation.
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PMID:Human immunodeficiency virus type 1-infected HL-60 cells are capable of both monocytic and granulocytic differentiation. 146 65

Single-cycle infections have been used to study the human immunodeficiency virus type 1 (HIV-1) life cycle in CD4+ T-cell lines that differ in their permissiveness for infection. In single-cycle infections of highly permissive C8166 cells, 50% of the infectious units escaped being blocked by a monoclonal antibody against the virus binding site on CD4 (leu3a) within 30 min. In contrast, 50% of the infectious units for three less permissive cell lines (H9, A3.01, and Jurkat) required 4 h to escape the leu3a block. Entry was also more efficient in the highly permissive cells, with NL4-3 stocks having three times more infectious units for C8166 cells than for H9, A3.01, or Jurkat cells. Postentry steps up through reverse transcription required approximately 3.5 h in each of the cell lines. The times lapsing between reverse transcription and the expression of reverse transcripts ranged from 17 to 25 h in the different cell lines. Virus production per cell was also similar in the different cell lines (within 1.5-fold of each other). These results indicate that a major determinant of the permissiveness of growing T cells for HIV-1 is the rate and efficiency of virus entry.
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PMID:Human immunodeficiency virus type 1 NL4-3 replication in four T-cell lines: rate and efficiency of entry, a major determinant of permissiveness. 167 69

The biologically cloned human immunodeficiency virus type 1 (HIV-1) RF isolate is sensitive to neutralization by the murine monoclonal antibody (MAb) G3-4 to a conformationally sensitive epitope in the V2 loop of HIV-1 gp120. To assess how variation in the V2 amino acid sequence affects neutralization by this MAb, we cultured RF in the presence of G3-4 to select neutralization escape mutants. Three such mutants resistant to G3-4 neutralization were generated from three independent experiments. Solubilized gp120 from each of these escape mutants had a reduced affinity for G3-4 and also for two other V2 MAbs that were able to bind the wild-type RF gp120. PCR sequencing of the entire gp120 of the wild-type RF virus and the escape mutants showed that amino acid substitutions had occurred only at two positions, Y177H and L179P, both in V2. Experimental introduction of the Y177H substitution into the RF V2 loop in the context of the NL4-3 molecular clone re-created the G3-4-resistant phenotype. The L179P mutant was not viable. Thus, our findings confirm that the HIV-1 V2 loop contains the conformationally sensitive neutralization epitope recognized by G3-4 and that a single amino acid substitution within this region can result in escape variants that arise from immune selection pressure.
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PMID:Characterization of mutants of human immunodeficiency virus type 1 that have escaped neutralization by a monoclonal antibody to the gp120 V2 loop. 750 88

Haemopoietic cytopenias are a frequent occurrence in human immunodeficiency virus type-1 (HIV-1) induced disease. In order to examine the possible direct inhibition of marrow haemopoiesis by HIV-1, we have investigated the effect of HIV-1 infection on myelopoiesis in long-term bone marrow cultures. In vitro exposure of normal marrow cultures to three different lymphocytotropic HIV-1 isolates resulted in productive infection, as demonstrated by a progressive increase of gag p24 antigen. In these experiments, ICR-3 isolate, but not LAV' or NL4-3 isolates, accelerated the loss of non-adherent cells. A differential ability of these HIV-1 isolates to suppress myelopoiesis was confirmed in long-term cultures in which virus was added continuously. In these cultures, ICR-3, and to a lesser extent also NL4-3, but not LAV', induced a progressive decrease in the number of total non-adherent cells as well as non-adherent colony forming units-granulocyte/macrophage (CFU-GM). Furthermore, exposure of normal purified CD34+ cells to ICR-3 induced defects in their ability to form haemopoietic colonies; this inhibitory effect was significantly relieved by pretreatment of ICR-3 with an anti-gp120 antibody. Similar exposure of CD34+ cells to LAV' and NL4-3 induced no such defects. These data indicate that some HIV-1 isolates can impair bone marrow haemopoiesis in a dose-dependent fashion, acting, at least in part, at the level of haemopoietic stem/progenitor cells.
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PMID:Effect of different human immunodeficiency virus type-1 (HIV-1) isolates on long-term bone marrow haemopoiesis. 751 Sep 92

To address the relationship between primary sequence variation in HIV-1 gp120 and its antigenic structure in a simple system, we have measured the binding of human and murine monoclonal antibodies (MAbs) to gp120 from four molecular clones of HIV-1 LAI: HxB2, HxB3, Hx10, and NL4-3. Despite the close relationship between these clones, and their relatively conserved gp120 sequences, there is considerable variation in their antigenic structure, judged by MAb reactivities to the V2, V3, and C4 domains and to discontinuous epitopes. Because of our prior studies of the determinants of MAb binding to HxB2 gp120, we can make reasonable estimates of how sequence variation among the LAI clone gp120s affects their binding of some MAbs; for other MAbs our current knowledge of gp120 structure is too limited to allow such estimates. These results indicate that small variations in primary gp120 amino acid sequence can profoundly affect recognition of this glycoprotein by all five groups of defined anti-gp120 neutralizing antibodies.
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PMID:Antigenic variation in gp120s from molecular clones of HIV-1 LAI. 751 94

The viral infectivity factor gene, vif of human immunodeficiency virus type 1 (HIV-1), is required for full infectivity in most T-cell lines. The replication kinetics exhibited by these mutants has been shown to be cell type-dependent. In H9 cells as well as primary lymphocytes, vif mutants are incapable of establishing infection. This has led to classification of these cell types as non-permissive for vif mutant replication. The T-cell lines Sup T1 and C8166 are able to replicate the vif mutant virus, leading to their classification as permissive for vif mutant replication. In this study, four cell lines (Sup T1, C8166, Molt 4 Clone 8, and A3.01) were tested for their ability to replicate vif mutant virus derived from two different strains of HIV-1 (HXB2 and NL4-3) that had been passaged on various cell lines. Although the kinetics of initial infection was delayed in all cells, by the second passage of vif mutant virus on Sup T1 or Molt 4 cells the kinetics of replication were identical to wild type virus. In contrast, mutant virus displayed delayed replication kinetics in C8166 and A3.01 cells in both initial and subsequent passages. In addition, the levels of viral DNA in infected Sup T1 cells were similar for delta vif and wild type virus, but in C8166 cells delta vif virus DNA levels were reduced compared to wild type virus. These results argue that in Sup T1 and Molt 4 cells there is a factor present that is able to complement the defect in vif mutant viruses which is absent or inefficient in its activity in C8166 and A3.01 cells.
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PMID:Complementation of human immunodeficiency virus type 1 vif mutants in some CD4+ T-cell lines. 752 73

The third variable domain (V3 domain) of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 contains a substantial number of positively charged amino acid residues. We previously demonstrated that mutation of basic amino acid residues at position 303, 306, 309, 313, and 325 in the V3 domain of HIV-1 strain NL4-3 resulted in a dramatic elimination of both virus infectivity and syncytium-inducing ability. Mutations of arginine at position 302 to serine (R302S) or lysine at position 320 to glutamine (K320Q) had variable effects on infectivity for a panel of T cell lines tested. These mutations are located on opposite sides of the Gly-Pro-Gly-Arg-Ala sequence in the center of the V3 domain. The R302S and K320Q mutations allowed us to determine if these basic residues are important for virus neutralization by polyanionic compounds. Dextran sulfate and heparin inhibited the cytopathogenicities of both mutants for MT-4 cells, although their 50% antiviral effective doses were slightly higher than those required to achieve complete protection against wild-type HIV-1NL4-3 replication. This result emphasizes that the basic amino acids of Arg302 and Lys320 are not essential for the inhibitory effect of dextran sulfate and heparin on HIV-1 infection.
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PMID:Single basic amino acid substitutions at position 302 or 320 in the V3 domain of HIV type 1 are not sufficient to alter the antiviral activity of dextran sulfate and heparin. 757 13

With the goal of examining the functional diversity of human immunodeficiency virus type 1 (HIV-1) env genes within the peripheral blood mononuclear cells of an asymptomatic individual, we substituted four complete env genes into the replication-competent NL4-3 provirus. Despite encoding full-length open reading frames for gp120 and gp41 and the second coding exon of tat and rev, each chimera was replication defective. Site-directed mutagenesis of codon 78 in the Rev activation domain (from a hitherto unique Ile to the subtype B consensus Leu) partially restored infectivity for two of three chimeras tested. Similarly, mutagenesis of rev codon 78 of NL4-3 from Leu to Ile partially attenuated this virus. Ile-78 was found in all 13 clones examined from samples taken from this asymptomatic subject 4.5 years after infection, including 9 from peripheral blood mononuclear cells and 4 from a virus isolate, as well as 4 additional clones each from peripheral blood mononuclear cells sampled 37 and 51 months later. We next examined conservation of the Rev activation domain within and among long-term survivors (LTS) and patients with AIDS, as well as T-cell-line-adapted strains of HIV-1. Putative attenuating mutations were found in a minority of sequences from all five LTS and two of four patients with AIDS. Of the 11 T-cell-line-adapted viruses examined, none had these changes. Among and within LTS virus population had marginally higher levels of diversity in Rev than in Env; patients with AIDS had similar levels of diversity in the two reading frames; and T-cell-line-adapted viruses had higher levels of diversity in Env. These results are consistent with the hypothesis that asymptomatic individuals harbor attenuated variants of HIV-1 which correlate with and contribute to their lack of disease progression.
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PMID:Persistence of attenuated rev genes in a human immunodeficiency virus type 1-infected asymptomatic individual. 763 19

Two DNA constructs encoding portions of the human immunodeficiency virus type-1 (HIV-1) genome have been used to raise antibody responses in BABL/c mice. One DNA (pNL4-3.env) expresses the natural form of the envelope glycoprotein (Env) of HIV-1-NL4-3 (NL4-3). The second (pNL4-3.dpol) produces noninfectious NL4-3 particles. These two DNAs (alone or in combination) raised only transient titers of anti-Env IgG. In the same group in which pNL4-3.dpol DNA raised only transient antibody responses to Env, this DNA raised persistent antibody responses to the p24 virion capsid protein (CA). Antibody responses to Env and CA also showed different abilities to be boosted. The final boosts of pNL4-3.dpol DNA increased titers of anti-CA antibody, but failed to boost the falling titers of anti-Env antibody. At peak titers of anti-Env activity, sera with relatively low ELISA titers of anti-Env IgG (end points of 1:6250) had good titers of neutralizing antibody (approximately 1:3800 for 50 TCID50 of NL4-3). At the end of the experiment (a time when anti-Env antibodies had fallen to near background levels), in vitro-restimulated splenocytes from both pNL4-3.env and pNL4-3.dpol DNA vaccine groups exhibited similar cytotoxic activity.
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PMID:Use of DNAs expressing HIV-1 Env and noninfectious HIV-1 particles to raise antibody responses in mice. 774 64

To understand how different cell types might influence the generation of viral variants, we have examined the differences in the viral life cycle of the HIV-1 isolate, NL4-3, in the human promyelocytic cell line, HL-60, and the human T cell line, H9. NL4-3 harvested from H9 cells productively infected and was cytopathic to H9 and HL-60 cells. However, the cytopathic effect was delayed in HL-60 cells compared to that seen in H9 cells, suggesting that NL4-3 replication was restricted in myeloid cells. This restriction was overcome by production of a variant virus, NL4-3 (M), which replicated efficiently in HL-60 cells. Measurements of the kinetics of entry of NL4-3 in H9 and HL-60 cells and NL4-3 (M) in HL-60 cells demonstrated that the timing of viral entry into each cell line was similar. However, quantitation of the amount of newly reverse-transcribed NL4-3 DNA in H9 and HL-60 cells revealed that NL4-3-infected H9 cells and NL4-3 (M)-infected HL-60 cells contained consistently more newly reverse-transcribed DNA than NL4-3-infected HL-60 cells. This difference was further amplified by inefficient spread of the virus throughout the HL-60 culture. Together these results suggest that the efficiency of NL4-3 infection of HL-60 cells is restricted at early steps in the viral life cycle and may be restricted at late steps as well.
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PMID:Restricted replication of the HIV-1 T-lymphotropic isolate NL4-3 in HL-60 cells. 783 19


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