Dual Infection of the Central Nervous System by AIDS Viruses with Distinct Cellular Tropisms

Koyanagi, Yoshio; Miles, Steven A.; Mitsuyasu, Ronald T.; Merrill, Jean E.; Vinters, Harry V.; Chen, Irvin S. Y.

doi:10.1126/science.3646751

Cited by 784 publications

(484 citation statements)

References 28 publications

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“…HIV-1 JR-CSF is a clinical strain provided by the National Institutes of Health AIDS research and reference reagent program (7). The virus was cultured with phytohemagglutinin (PHA)-activated PBMCs for 6 days.…”

Section: Methodsmentioning

confidence: 99%

Highly purified CD25⁻resting T cells cannot be infectedde novowith HIV-1

Chou

Ramilo

Vitetta

1997

Proc. Natl. Acad. Sci. U.S.A.

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Previous studies have demonstrated that the expression of CD25 can distinguish CD25 ؊ latently infected cells from CD25 ؉ cells actively producing virus. Our studies were designed to characterize the nature and stability of the viral genome in CD25 ؊ quiescent HIV-1-infected cells and to determine whether these cells could be infected Using a model of acute in vitro infection, we have previously demonstrated that the expression of CD25 can distinguish latently infected cells (CD25 Ϫ ) from cells actively producing virus (CD25 ϩ ) (1) and that these two populations display significant differences with regard to the nature of the proviral genome. Thus, by combining the use of a potent anti-CD25 immunotoxin and sensitive immunofluorescence staining we have obtained highly purified resting cells. This is important because interpretations of viral latency have been confounded, in part, by the degree of purity of the resting cells. Indeed, partially reverse-transcribed DNAs (2, 3), full-length extrachromosomal DNA (4, 5), and stable integrated viral genomes (6) have been reported to occur in resting peripheral blood mononuclear cells (PBMCs). Although these differences can be explained in part by the different methodologies employed, they could also suggest the existence of several subsets of latently infected cells and possibly the contamination of resting cells with activated ones.Using our in vitro model of acute HIV-1 infection, the present studies were designed to characterize the nature and stability of the viral genome in quiescent HIV-1-infected CD25 Ϫ cells and to determine whether CD25 Ϫ cells can be infected de novo. The results of these analyses have implications regarding the origin of latently infected cells. MATERIALS AND METHODSVirus Strain and Standard Inoculum. HIV-1 JR-CSF is a clinical strain provided by the National Institutes of Health AIDS research and reference reagent program (7). The virus was cultured with phytohemagglutinin (PHA)-activated PBMCs for 6 days. The culture supernatant was purified on an Amicon concentrator (Centriprep 100) by centrifugation at 500 ϫ g at 4ЊC for 1 hr to remove cytokines and mitogens (M r Ͻ100 kD). This standard inoculum was adjusted to 10 times its original concentration, aliquoted, and stored at Ϫ80ЊC.Purification of CD4 ؉ CD25 ؊ Human Quiescent T Lymphocytes. Fresh PBMCs were obtained from normal healthy donors by centrifugation over Ficoll͞Hypaque and were cultured in RPMI 1640 supplemented with 5% autologous plasma [complete-medium (CM)] for 18 hr to remove peripheral blood macrophages by plastic adhesion. Adherent cells were used for additional experiments. The nonadherent cells were further cultured under the same conditions for 2 hr, and were treated with 5 mM leucine methyl ester in RPMI 1640 for 1 hr at 25ЊC to further deplete the macrophages and natural killer cells (8). CD4 ϩ T cells were purified by positive selection on anti-CD4-coated magnetic beads (Dynal, Great Neck, NY) according to the instructions of the manufacturer. By trypan blue...

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Section: Methodsmentioning

confidence: 99%

Highly purified CD25⁻resting T cells cannot be infectedde novowith HIV-1

Chou

Ramilo

Vitetta

1997

Proc. Natl. Acad. Sci. U.S.A.

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“…HIV-1 replication in macrophages. The JRFL strain of HIV-1 was prepared by transfecting the infectious proviral plasmid 40 into 293T cells. The transfection was performed using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA) as described previously.…”

Section: Figure 4 Phosphorylation Levels Of Signal Molecules In Il-34mentioning

confidence: 99%

IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation

et al. 2010

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Macrophage colony-stimulating factor (M-CSF) regulates the production, survival and function of macrophages through Fms, the receptor tyrosine kinase. Recently, interleukin-34 (IL-34), which shares no sequence homology with M-CSF, was identified as an alternative Fms ligand. Here, we provide the first evidence that these ligands indeed resemble but are not necessarily identical in biological activity and signal activation. In culture systems tested, IL-34 and M-CSF showed an equivalent ability to support cell growth or survival. However, they were different in the ability to induce the production of chemokines such as MCP-1 and eotaxin-2 in primary macrophages, the morphological change in TF-1-fms cells and the migration of J774A.1 cells. Importantly, IL-34 induced a stronger but transient tyrosine phosphorylation of Fms and downstream molecules, and rapidly downregulated Fms. Even in the comparison of active domains, these ligands showed no sequence homology including the position of cysteines. Interestingly, an anti-Fms monoclonal antibody (Mab) blocked both IL-34-Fms and M-CSF-Fms binding, but another MAb blocked only M-CSF-Fms binding. These results suggested that IL-34 and M-CSF differed in their structure and Fms domains that they bound, which caused different bioactivities and signal activation kinetics/strength. Our findings indicate that macrophage phenotype and function are differentially regulated even at the level of the single receptor, Fms.

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“…Different strains vary in infectivity for primary macrophages (m~), rate of replication and syncytium-forming capacity and the evolution of these properties probably influences the pathogenesis of HIV infection (Asjo et al, 1986;Fenyo et al, 1988;Collman et al, 1989;Tersmette et al, 1989;Schuitemaker et al, 1991). Recent evidence suggests that m~b tropism is a fundamental property of HIV, since m~b-tropic strains of HIV are detectable in the peripheral blood at all stages of disease (Gendelman et al, , 1990Massari et al, 1990;Schuitemaker et al, 1991) and viruses isolated from tissue sites appear to possess higher m~b tropism than those from the peripheral blood (Gartner et al, 1986;Koyanagi et al, 1987;Cheng-Mayer et al, 1989;Gendelman et al, 1990;Schuitemaker et al, 1992). However, the relationship between m~b tropism in vitro and the pathogenesis of HIV infection remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Definition of the range and distribution of human immunodeficiency virus macrophage tropism using PCR-based infectivity measurements

Collin

Illei

James

et al. 1994

Journal of General Virology

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The tropism of human immunodeficiency virus (HIV) for macrophages (m~b) is a well recognized phenomenon, but the range and distribution of m~b-tropic phenotypes have not been defined by quantitative means. This study uses a PCR-based infectivity assay to derive an index of m~ tropism for several common strains of HIV. The results show that m~b tropism varies over about six orders of magnitude and that the most m~b-tropic strains have a higher infectivity for m~b than for peripheral blood lymphocytes. Strains were distributed throughout this range, suggesting that m~b tropism is a continuously variable phenotypic property. Although the degree of tropism was strongly influenced by the mode of isolation and propagation of virus strains, there was no evidence for the existence of distinct m~b-tropic or non-m~b-tropic phenotypes. Finally, the tropism of two selected strains was found to be determined by an early step in replication, probably virus entry.

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Dual Infection of the Central Nervous System by AIDS Viruses with Distinct Cellular Tropisms

Cited by 784 publications

References 28 publications

Highly purified CD25⁻resting T cells cannot be infectedde novowith HIV-1

Highly purified CD25⁻resting T cells cannot be infectedde novowith HIV-1

IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation

Definition of the range and distribution of human immunodeficiency virus macrophage tropism using PCR-based infectivity measurements

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Dual Infection of the Central Nervous System by AIDS Viruses with Distinct Cellular Tropisms

Cited by 784 publications

References 28 publications

Highly purified CD25−resting T cells cannot be infectedde novowith HIV-1

Highly purified CD25−resting T cells cannot be infectedde novowith HIV-1

IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation

Definition of the range and distribution of human immunodeficiency virus macrophage tropism using PCR-based infectivity measurements

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Product

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Highly purified CD25⁻resting T cells cannot be infectedde novowith HIV-1

Highly purified CD25⁻resting T cells cannot be infectedde novowith HIV-1