Selective permissiveness of TPA differentiated THP-1 myelomonocytic cells for human cytomegalovirus strains AD169 and Towne

Turtinen, Lloyd W.; Seufzer, Bradley J.

doi:10.1006/mpat.1994.1037

Cited by 35 publications

(39 citation statements)

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“…3E). Undifferentiated cultures did not produce virus (data not shown), as expected from previous studies with THP-1 cells (42,88,91,92). In contrast, Towne-BAC was recovered from THP-1 cells differentiated for 1, 3, 5, or 7 days prior to infection (Fig.…”

Section: Vica-deficient Virus Replication and Cell Death Suppressor Esupporting

confidence: 87%

“…THP-1 cells, obtained from Patricia Kowalczyk, Emory University, were cultured in RPMI 1640 medium (Invitrogen, Carlsbad, CA) supplemented with 10% fetal bovine serum (Atlanta Biologicals, Norcross, GA). To induce differentiation, cells were treated with 20 nM 12-Otetradecanoylphorbol 13-acetate (TPA) and 50 M hydrocortisone (HC) (both from Sigma, St. Louis, MO) as previously reported for HCMV infections (42,88,91). Isolation of ⌬UL36, Towne-BAC (where BAC is bacterial artificial chromosome), and RC2940 strains and plaque purification of TownevarRIT3 from TownevarRIT were previously reported (20,28,51,73).…”

Section: Methodsmentioning

confidence: 99%

“…Similar results were obtained from cultures treated with TPA only but were not apparent in cultures treated by HC only (data not shown). Cultures treated with the pan-caspase inhibitor (42,88,91,92). Combined, these observations suggested that THP-1 cells could be used to evaluate responses to HCMV infection within monocytes at different stages of caspase-dependent differentiation to macrophages.…”

Section: Vica-deficient Virus Replication and Cell Death Suppressor Ementioning

confidence: 95%

“…Morphological and functional characteristics, expression of membrane antigens and receptors, and transcriptional analyses have all highlighted similarities to the differentiation pathway of primary cells (2,35,44,49,85,86). When treated with the phorbol ester TPA and HC to optimize HCMV replication (42,88,91,92), THP-1 cells became loosely adherent within the first 24 h and remained spherical (Fig. 3A).…”

Section: Vica-deficient Virus Replication and Cell Death Suppressor Ementioning

confidence: 99%

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The Human Cytomegalovirus UL36 Gene Controls Caspase-Dependent and -Independent Cell Death Programs Activated by Infection of Monocytes Differentiating to Macrophages

McCormick

Roback

Livingston-Rosanoff

et al. 2010

J Virol

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The cellular protease caspase-8 activates extrinsic apoptosis and also functions to promote monocyteto-macrophage differentiation. Differentiation-induced alterations to antiviral caspase-8-dependent cell death pathways are unclear. Here, we show THP-1 monocyte-to-macrophage differentiation alters the specific cell death pathways activated in response to human cytomegalovirus (HCMV) infection. Employing viruses with mutations in UL36, the gene that encodes the viral inhibitor of caspase-8 activation (vICA), our data indicate that both caspase-dependent and -independent death pathways are activated in response to infection. Activation of caspase-dependent and -independent cell death responses restricted growth of vICA-deficient viruses, and vICA/pUL36 inhibited either response. Thus, these studies also reveal that the UL36 gene controls a caspase-independent cell death pathway. The impact of caspases on control of antiviral responses differed at early and late stages of macrophage differentiation. Early in differentiation, vICA-deficient virus-induced cell death was dependent on caspases and inhibited by the pan-caspase inhibitor z-VAD(OMe)-fluoromethyl ketone. In contrast, virus-induced death at late times of differentiation was caspase independent. Additional unlabeled and fluorescent inhibitors indicated that caspase-8 promoted death from within infected cells at early but not late stages of differentiation. These data highlight the multifunctional role of vICA/pUL36 as HCMV encounters various antiviral responses during macrophage differentiation.Based on the frequency of infected cells in patients with disseminated disease, monocytes and monocyte-derived macrophages are important to the pathogenesis of human cytomegalovirus (HCMV) (8,24,32). Further, peripheral blood monocytes and granulocyte-macrophage progenitors are suggested to be latent reservoirs as healthy seropositive individuals carry HCMV DNA in these cells, a result consistent with the maintenance of latent genomes within experimentally infected progenitors (6,37,38,58,72,76,79,80). Infected monocytes do not produce new virus; however, replication follows monocyte-macrophage differentiation whether induced by growth or proinflammatory cytokines or allogeneic stimulation. Evidence suggests that monocyte infections promote differentiation to a permissive, proinflammatory macrophage (14, 74). Thus, the production of new progeny is highly dependent on cellular differentiation. Monocytes, cells undergoing macrophage differentiation, and mature macrophages differ in the expression patterns of specific genes, including those important to cell death control (44, 49). Whether any change in expression of cell death control genes influences cell death pathways activated by HCMV infection is unclear. The current study addresses this question by evaluating the requirement for one viral cell death suppressor during productive infection of monocytes at different stages of macrophage differentiation.HCMV and the related murine cytomegalovirus (MCMV) encode several...

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Section: Vica-deficient Virus Replication and Cell Death Suppressor Esupporting

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Vica-deficient Virus Replication and Cell Death Suppressor Ementioning

confidence: 95%

Section: Vica-deficient Virus Replication and Cell Death Suppressor Ementioning

confidence: 99%

See 2 more Smart Citations

The Human Cytomegalovirus UL36 Gene Controls Caspase-Dependent and -Independent Cell Death Programs Activated by Infection of Monocytes Differentiating to Macrophages

McCormick

Roback

Livingston-Rosanoff

et al. 2010

J Virol

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“…While these studies have proven instrumental, these model systems possess characteristics that render studies assessing complete reactivation from latency problematic. In vitro HCMV latency models using either THP-1 cells (a monocyte cell line) (10) or NTera2 cells (embryonic carcinoma cell line) (2) have been extensively employed to study HCMV latency (5,10,11,20,25,30,31,34,45,62,65,69). While these cell lines are valuable tools for identifying cellular factors that modulate viral latency, the cell types do not maintain the viral genome for extended periods of time, resulting in no clear demarcation between latency and reactivation.…”

mentioning

confidence: 99%

A Myeloid Progenitor Cell Line Capable of Supporting Human Cytomegalovirus Latency and Reactivation, Resulting in Infectious Progeny

O’Connor

Murphy

2012

J Virol

112

159

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Human cytomegalovirus (HCMV) is a herpesvirus that establishes a lifelong, latent infection within a host. At times when the immune system is compromised, the virus undergoes a lytic reactivation producing infectious progeny. The identification and understanding of the biological mechanisms underlying HCMV latency and reactivation are not completely defined. To this end, we have developed a tractablein vitromodel system to investigate these phases of viral infection using a clonal population of myeloid progenitor cells (Kasumi-3 cells). Infection of these cells results in maintenance of the viral genome with restricted viral RNA expression that is reversed with the addition of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA, also known as PMA). Additionally, a latent viral transcript (LUNA) is expressed at times where viral lytic transcription is suppressed. Infected Kasumi-3 cells initiate production of infectious virus following TPA treatment, which requires cell-to-cell contact for efficient transfer of virus to other cell types. Importantly, lytically infected fibroblast, endothelial, or epithelial cells can transfer virus to Kasumi-3 cells, which fail to initiate lytic replication until stimulated with TPA. Finally, inflammatory cytokines, in addition to the pharmacological agent TPA, are sufficient for transcription of immediate-early (IE) genes following latent infection. Taken together, our findings argue that the Kasumi-3 cell line is a tractablein vitromodel system with which to study HCMV latency and reactivation.

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Cell membrane bound N-acetylneuraminic acid is involved in the infection of fibroblasts and phorbol-ester differentiated monocyte-like cells with human cytomegalovirus (HCMV)

Lobert

Hober

Dewilde

et al. 1995

Archives of Virology

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We focused on the role of membrane bound sugar residues in the infection of fibroblasts and monocyte-like cells with human cytomegalovirus (HCMV). Treatment of phorbol 12-myristate 13-acetate (PMA) differentiated monocyte-like cells THP-1 or human fibroblasts MRC-5 with lectins specific for N-acetylneuraminic acid (NeuAc) blocked infection with HCMV. HCMV failed to infect sialidase-treated differentiated THP-1 cells or MRC-5 cells. By using NeuAc, N-glycolylneuraminic acid (NeuGl) and alpha 2-3, but not alpha 2-6, sialyl-oligosaccharide, the infection of cells was less efficient. NeuAc was more potent inhibitor than NeuGl. These observations suggest that the sialic acid specificity and the nature of the interglycosidic linkage at the end of the complex carbohydrates may play an important role. Analogous experiments indicated that HCMV binds to N-acetylglucosamine (GlcNAc) in addition to NeuAc. Human cytomegalovirus infection in differentiated THP-1 cells and in human fibroblasts was inhibited by incubation of the virus with 20 micrograms/ml of heparin before and during the adsorption period. Treatment of the cells with heparinase or heparitinase inhibited infection with HCMV. We emphasized the role of NeuAc and GlcNAc and heparan sulfate proteoglycans at the surface of the cells, in the early steps of infection of both human fibroblasts and PMA differentiated monocyte-like cells with HCMV.

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Selective permissiveness of TPA differentiated THP-1 myelomonocytic cells for human cytomegalovirus strains AD169 and Towne

Cited by 35 publications

References 0 publications

The Human Cytomegalovirus UL36 Gene Controls Caspase-Dependent and -Independent Cell Death Programs Activated by Infection of Monocytes Differentiating to Macrophages

The Human Cytomegalovirus UL36 Gene Controls Caspase-Dependent and -Independent Cell Death Programs Activated by Infection of Monocytes Differentiating to Macrophages

A Myeloid Progenitor Cell Line Capable of Supporting Human Cytomegalovirus Latency and Reactivation, Resulting in Infectious Progeny

Cell membrane bound N-acetylneuraminic acid is involved in the infection of fibroblasts and phorbol-ester differentiated monocyte-like cells with human cytomegalovirus (HCMV)

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