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Query: UMLS:C0021051 (immunodeficiency)
 71,517 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

Isolates of human immunodeficiency virus type 1 (HIV-1) undergo many different rates of replication, with the time course of replication being determined by the host cell and the virus. Recently, we demonstrated that the permissiveness of four CD4+ T-cell lines for the laboratory strain NL4-3 correlated with the rate and efficiency of virus entry. In this study, we have analyzed the replication of a "slow/low" isolate from the pre-AIDS period of infection and two "rapid/high" isolates from the AIDS period of infection to determine which steps in the virus life cycle determine differences in the growth characteristics of patient isolates. Differences in the growth of the patient isolates correlated with differences in entry but not postentry steps of the virus life cycle. The two rapid/high patient isolates (SF33 and SF216) underwent 50% entry in less than or equal to 0.5 hr in C8166 cells, in less than or equal to 1 hr in mitogen-stimulated peripheral blood mononuclear cells, and in greater than or equal to 2.5 hr in H9 cells. In contrast, a class 3 slow/low patient isolate required 1 hr for 50% entry into C8166 cells, 3 hr for 50% entry into peripheral blood mononuclear cells, and 5-6 hr for 50% entry into H9 cells. Entry efficiency correlated with entry rate, with the rapid/high viruses having a 2-fold higher titer and the slow/low virus having a 5-fold higher titer on C8166 than H9 cells. The laboratory strain NL4-3 displayed intermediate rates and efficiencies of entry. These data demonstrate that entry characteristics are major determinants of the pathogenic potential of patient isolates.
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PMID:Replication of patient isolates of human immunodeficiency virus type 1 in T cells: a spectrum of rates and efficiencies of entry. 154 86

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

Profound differences exist in the replicative capacities of various human immunodeficiency virus 1 isolates in primary human monocytes. To investigate the molecular basis for these differences, recombinant full-length clones were constructed by reciprocal DNA fragment exchange between a molecular clone derived from a monocyte-tropic isolate (ADA) and portions of two full-length clones incapable of infection or replication in primary monocyte cultures (HXB2 and NL4-3). Virions derived from proviral clones that contained ADA sequences encoding vpu and the N and C termini of the surface envelope glycoprotein (gp120) were incapable of replication in monocytes. However, a 283-base-pair ADA sequence encoding amino acids 240-333 of the mature gp120 protein conferred the capacity for high-level virus replication in primary monocytes. The predicted amino acid sequence of this ADA clone differed from NL4-3 and HXB2 at 22 of 94 residues in this portion of gp120, which includes the entire third variable domain. Only 2 of 11 residues implicated in CD4 binding are located in this region of gp120 and are identical in HXB2, NL4-3, and ADA. Alignment of the ADA sequence with published amino acid sequences of three additional monocyte-replicative and three monocyte-nonreplicative clones indicates 6 discrete residues with potential involvement in conferring productive human immunodeficiency virus 1 infection of primary monocytes.
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PMID:Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes. 201 29

We describe the isolation and characterization of variant cell lines which are chronically infected with the human immunodeficiency virus (HIV) and resistant to the action of immunotoxins directed against the HIV envelope protein. These variants all produce normal levels of HIV proteins, budding virions, and the envelope protein precursor gp160. Two of the variants, 10E and 11E, contain a mutation within the env gene which results in the production of a truncated precursor and altered processing and transport of the protein to the cell surface. Variants B9 and G4 are defective in gp160 cleavage and do not efficiently transport the envelope protein to the cell surface. There are no mutations in the expressed viruses of B9 and G4. These cell lines express higher levels of CD4 protein and mRNA than H9/NL4-3. Thus, 10E, 11E, B9, and G4 have escaped immunotoxin action by downmodulating the envelope protein from their cell surfaces. None of these variants produce infectious HIV. Two other immunotoxin-resistant variants, E9-3 and 41-17, produce normal levels of gp160, efficiently transport the cleaved and processed subunits to the cell surface, and secrete infectious HIV. These studies identify alterations in gp160 processing that underscore the importance of the relationship between HIV and the cell that it infects.
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PMID:Processing of the envelope glycoprotein gp160 in immunotoxin-resistant cell lines chronically infected with human immunodeficiency virus type 1. 747 32

The human immunodeficiency virus type 1-specific Vpu protein is a small integral membrane phosphoprotein that induces degradation of the virus receptor CD4 in the endoplasmic reticulum and, independently, increases the release of progeny virions from infected cells. To address the importance of Vpu for virus replication in primary human cells such as peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (MDM), we used three different sets of monocyte-tropic molecular clones of human immunodeficiency virus type 1: a primary isolate, AD8+, and two chimeric variants of the T-cell-tropic isolate NL4-3 carrying the env determinants of either AD8+ or SF162 monocyte-tropic primary isolates. Isogenic variants of these chimeric viruses were constructed to express either wild-type Vpu or various mutants of Vpu. The effects of these mutations in the vpu gene on virus particle secretion from infected MDM or PBMC were assessed by determination of the release of virion-associated reverse transcriptase into culture supernatants, Western blot (immunoblot) analysis of pelleted virions, and steady-state or pulse-chase metabolic labeling. Wild-type Vpu increased virus release four- to sixfold in MDM and two- to threefold in PBMC, while nonphosphorylated Vpu and a C-terminal truncation mutant of Vpu were partially active on virus release in primary cells. These results demonstrate that Vpu regulates virus release in primary lymphocyte and macrophage cultures in a similar manner and to a similar extent to those previously observed in HeLa cells or CD4+ T-cell lines. Thus, our findings provide evidence that Vpu functions in a variety of human cells, both primary cells and continuous cell lines, and mutations in Vpu affect its biological activity independent of the cell type and virus isolate used.
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PMID:Augmentation of virus secretion by the human immunodeficiency virus type 1 Vpu protein is cell type independent and occurs in cultured human primary macrophages and lymphocytes. 749 79

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

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


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