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

We have analyzed the phenotype of five human monocytoid cell lines (U-937, THP-1, RC.2A, Mono Mac 6, and DD) and their capacity to support replication of HIV-1 strains with known tropism for T lymphocytes and mononuclear phagocytes. HIV-1 Ba-L, a prototype monocytotropic HIV-1 strain, was unable to establish continuous replication in any of the cell lines used. In contrast, the lymphotropic strain IIIB could replicate in all CD4-positive cell lines. We conclude that the capacity of HIV-1 isolates to replicate in established human monocytoid malignant cells does not correlate with the tropism of the virus for primary mononuclear phagocytes. Since monocytoid cell lines do not distinguish HIV-1 variants tropic for mononuclear phagocytes, we suggest the use of primary cells for studies of HIV-1 tropism.
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PMID:Tropism for primary monocytes and for monocytoid cell lines are separate features of HIV-1 variants. 808 93

Manifestations of HIV-1 infection such as fever, hypergammaglobulinemia, and interstitial pneumonitis may be due to increased production of inflammatory cytokines such as interleukin-1 and interleukin-6 (IL-6). Monocytes/macrophages of HIV-1-infected individuals have been noted to produce increased amounts of IL-6, as well as to have enhanced accessory cell function. These studies examined the ability of HIV-1 tat, an important HIV-1 regulatory gene, to modulate monocyte/macrophage function. In these experiments, HIV-1 tat-transfected THP-1 cells, a monocytic cell line, enhanced THP-1 immune accessory cell function in the presence of pokeweed mitogen and concanavalin A. HIV-1 tat-transfected cells also increased production of lipopolysaccharide-stimulated IL-6 mRNA and IL-6 protein. The ability of monocytes/macrophages to support HIV-1 production while exhibiting little or no cytopathic effects allows these cells to serve as a reservoir for the virus. The ability of HIV-1 tat to regulate cellular function in monocytes/macrophages may play an important part in the pathogenesis of HIV-1 infection.
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PMID:Modulation of accessory cell function and interleukin-6 production by the HIV-1 tat gene. 817 23

We previously demonstrated that chronic infection of a monocytic cell line (U-937) with human immunodeficiency virus type 1 (HIV-1) was not accompanied by down-modulation of CD4 transcription, unlike the situation with CD4+ T lymphocyte lines. To better understand the refractoriness of monocytes to alterations in levels of CD4 mRNA, we treated HIV-IIIB chronically infected U-937 cells with phorbol myristate acetate (PMA), a known stimulus of HIV gene expression. Although PMA caused a significant increase in HIV mRNA levels that was sustained over 7 days, no effect on CD4 transcript levels was noted. Clonal derivatives of HIV-IIIB-infected U-937 cells, which produced a variety of infectious and defective particles, were likewise not affected in ability to produce CD4 mRNA. To rule out the possibility that U-937 cells select out HIV-1 variants unable to modulate CD4 mRNA levels, we passaged infectious virus from a U-937 clonal derivative (UHC1) onto different monocytic and T lymphocytic cell lines. In monocytic cell lines (U-937, PLB-985, THP-1), we observed an avirulent infection that did not affect CD4 mRNA levels, whereas UHC1 infection of each of two T lymphocytic cell lines (CEM-T4, Jurkat) caused both cytopathic replication and reductions in CD4 mRNA levels. In one case (Jurkat), variants expressing low CD4 mRNA may have emerged, because the outgrowth no longer expressed viral products. In the other case (CEM-T4), high expression of viral genes was accompanied by CD4 mRNA down-modulation, suggesting either that low-CD4-expressing variants were selected that maintained viral gene expression or that CD4 gene expression was repressed by viral products.
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PMID:HIV-1 associated down-modulation of CD4 gene expression is differentially restricted in lymphocytic and monocytic cell lines. 818 37

The myeloid-monocytic cells ML-1, HL-60, THP-1 and U-937 were chronically infected (for more than 2 years) with the lymphotropic HIV-1 strain HTLV-IIIB. Reinfection experiments revealed that viruses obtained from chronically infected ML-1/HIV-1 and HL-60/HIV-1 cells show a low infectivity if tested with uninfected ML-1 and HL-60 cells in contrast to virus preparations from chronically infected THP-1/HIV-1 and U-937/HIV-1 with their corresponding uninfected cell lines. Analyses of selected cell surface markers showed a differential expression of CD4, CD8, CD11c, CD14, CD15, CD20, HLA-DR and HLA-DQ in non- or chronically infected cells. During chronical infection, the myeloid-monocytic cells lost their reactivity with peroxidase and esterase. In chronically infected cells, the steady-state levels for TNF-alpha mRNA remained unchanged while those for IL-6 decreased. The half-lives of transcripts of both TNF-alpha (t1/2: 70 min) and IL-6 (t1/2: 100 min) were nearly the same in uninfected and chronically infected HL-60 cells.
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PMID:Characterization of cells of the myeloid-monocytic lineage (ML-1, HL-60, THP-1, U-937) chronically infected with the human immunodeficiency virus-1. 821 36

Toxoplasma gondii infection may be clinically silent in immunocompetent individuals but may cause fatal disease in immunocompromised patients such as those with HIV infection. Proinflammatory cytokines are known to be important in murine resistance to T. gondii but there are no data from human models of infection. We have investigated whether phagocytosis of T. gondii, of Mycobacterium tuberculosis (a pathogen which elicits a granulomatous host immune response) and of inert latex particles by THP-1 cells, a human monocytic line, caused gene expression and secretion of tumour necrosis factor (TNF), IL-6 and IL-8. These cytokines are important in recruitment and activation of T lymphocytes, and both TNF and IL-6 may have direct antitoxoplasmacidal and antimycobacterial activity. Phagocytosis of T. gondii by THP-1 cells resulted in minimal gene expression and secretion of TNF, IL-6 and IL-8 similar to that following phagocytosis of inert latex particles. In contrast, phagocytosis of M. tuberculosis resulted in increased gene expression of TNF and IL-8 as well as increased secretion of all three cytokines, particularly IL-8. These observations may partially explain the frequency of non-inflammatory host responses to T. gondii in immunocompetent individuals.
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PMID:Differential cytokine gene expression and secretion after phagocytosis by a human monocytic cell line of Toxoplasma gondii compared with Mycobacterium tuberculosis. 842 93

The prototypic macrophage-tropic HIV-1 isolate, HIV-1BaL, cannot replicate in the monocytoid cell line THP-1. After induction of differentiation by a phorbol diester, a fraction of THP-1 cells became permissive to HIV-1BaL. In contrast, this treatment decreased permissiveness for the lymphotropic isolate HIV-1LAI. Viral DNA was not synthesized in unstimulated THP-1 cells, as determined with PCR, suggesting that the block to HIV-1BaL replication in these cells occurred at an early step of the virus replicative cycle prior to or at the level of reverse transcription. Virus binding studies showed that differences in cell permissiveness for HIV-1BaL were not due to altered virus binding. Substantial amounts of HIV-1BaL bound to both undifferentiated and differentiated THP-1 cells, and this binding could not be prevented by blocking with the anti-CD4 antibody Leu3a, which did prevent the binding of HIV-1LAI to CEM T lymphoid cells. While Leu3a was very effective at preventing the infection by HIV-1LAI in CEM cells, it was less effective in preventing HIV-1BaL infection of differentiated THP-1 cells or primary macrophages. Although it is likely that molecules other than CD4 on monocytic cells can mediate binding of macrophage-tropic HIV, the binding of HIV-1BaL to THP-1 cells was not sufficient for infection, because binding was the same in nonpermissive undifferentiated cells as in permissive differentiated cells. Thus, the restriction of viral replication in this model cell system occurs at some step after virion binding. Comparison of differentiated THP-1 cells with their undifferentiated counterparts may provide an approach to defining cellular determinants of HIV host range other than CD4 expression and to characterizing the incompletely defined steps of viral entry.
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PMID:In vitro differentiation of monocytoid THP-1 cells affects their permissiveness for HIV strains: a model system for studying the cellular basis of HIV differential tropism. 843 70

THP-1 monocytoid cells, either not infected or chronically infected with human immunodeficiency virus type 1 (HIV-1), were challenged with Toxoplasma gondii. Parasitic growth, as assessed by trophozoite counting and measurement of supernatant p30 membrane antigen, was similar in HIV-infected and noninfected THP-1 cells. Also, T. gondii did not affect HIV replication. These experiments therefore failed to demonstrate any interaction between HIV-1 and T. gondii replication in concurrently infected monocytoid cells.
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PMID:Interaction between human immunodeficiency virus and Toxoplasma gondii replication in dually infected monocytoid cells. 845 71

A long-term, noncytopathic, productive infection of the monocytic leukemia cell line THP-1 with human immunodeficiency virus type 1 (HIV-1IIIB) was established. Both infected cells (THP-1/HIV-1IIIB) growing in suspension and uninfected, phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells, which are adherent, showed ultrastructural characteristics of differentiated cells. PMA-treated THP-1 cells could not be productively infected with HIV-1IIIB. THP-1/HIV-1IIIB cells produced virions mainly by budding at the plasma membrane. These cells retained the ability to differentiate into macrophage-like cells, capable of releasing the virus for extended periods of time (e.g., 40 days). PMA-mediated differentiation of THP-1/HIV-1IIIB cells modified the pattern of virus localization. Immediately after PMA treatment mature viral particles were primarily observed extracellularly. After 21 days in culture, however, the virions accumulated in intracellular vacuoles. THP-1/HIV-1IIIB cells may be used as a useful model system for HIV-infected macrophages.
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PMID:Long-term noncytopathic productive infection of the human monocytic leukemia cell line THP-1 by human immunodeficiency virus type 1 (HIV-1IIIB). 846 Apr 91

Mononuclear phagocytes infected with human immunodeficiency virus 1 (HIV-1) produce soluble factors that kill neurons in culture. To define the molecular events that lead to neuron killing, HIV-1 proteins were tested for the ability to trigger release of neurotoxins from human monocytes and lymphocytes. None of the recombinant-derived HIV-1 proteins examined (reverse transcriptase, protease, gag, nef, or gp120) were directly neurotoxic at concentrations from 100 pM to 10 nM. The envelope glycoprotein gp120 did, however, stimulate both isolated human blood monocytes and the monocytoid line THP-1 (but not lymphocytes or the lymphoid cell line H9) to discharge neurotoxic factors. These toxins consisted of heat-stable, protease-resistant molecules (< 500 Da) that copurified with neurotoxins from HIV-1-infected THP-1 cells and were blocked by antagonists to N-methyl-D-aspartate receptors. Release of neurotoxins through gp120 stimulation involved monocytoid CD4 receptors because toxin production could be inhibited either by a monoclonal antibody to the CD4-binding region of gp120 or by soluble CD4 receptors. Alternatively, production of neuron-killing factors could be induced with a peptide from the CD4-binding region of gp120. These data show that the HIV-1 envelope glycoprotein alone can stimulate neurotoxin release by binding to CD4 receptors of mononuclear phagocytes. Such neurotoxic factors may, in turn, contribute to the central nervous system dysfunction associated with HIV-1 by acting on neurons through N-methyl-D-aspartate receptors.
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PMID:The envelope glycoprotein of human immunodeficiency virus type 1 stimulates release of neurotoxins from monocytes. 846 87

Human immunodeficiency virus 2 (HIV-2) ISY and the newly derived HIV-2KR are infectious molecular clones that yield viruses differing markedly in their abilities to infect and/or induce syncytia in various T- and monocytoid-cell lines. Chimeric viruses were constructed from these two viral genomes to localize the genetic determinants of some of these properties. Envelope sequences, particularly those spanning the CD4 binding site, appear to be critical for the ability of HIV-2KR to infect MOLT-4 clone 8 and SupT1 cells and to efficiently infect the H9 cell line. On the other hand, multiple determinants may contribute to cytopathicity (gp41 and nef) in H9 cells and replication efficiency in monocytic (THP-1) cells.
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PMID:Mapping the determinants of human immunodeficiency virus 2 for infectivity, replication efficiency, and cytopathicity. 848 38


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