Development of a fluorescence-based assay to screen antiviral drugs against Kaposi's sarcoma–associated herpesvirus

Nun, Tamara K.; Kroll, David J.; Oberlies, Nicholas H.; Soejarto, Djaja D.; Case, Ryan; Piskaut, Pius; Matainaho, Teatulohi; Hilscher, Chelsey; Dittmer, Dirk P.; Gao, Shou‐Jiang; Damania, Blossom

doi:10.1158/1535-7163.mct-07-0108

Cited by 14 publications

(9 citation statements)

References 51 publications

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“…To confirm that the presence of the KSHV genome is responsible for the induction of IFI16 association with ASC and caspase-1, we employed a stably selected recombinant KSHV-infected BJAB-KSHV cell line (13). We observed IFI16 and ASC in the caspase-1 immunoprecipitates only in KSHV-positive BJAB cells and not in KSHV-negative parental BJAB cells (Fig.…”

Section: Resultsmentioning

confidence: 87%

Kaposi's Sarcoma-Associated Herpesvirus Latency in Endothelial and B Cells Activates Gamma Interferon-Inducible Protein 16-Mediated Inflammasomes

Singh

Kerur

Bottero

et al. 2013

J Virol

140

146

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Section: Resultsmentioning

confidence: 87%

Kaposi's Sarcoma-Associated Herpesvirus Latency in Endothelial and B Cells Activates Gamma Interferon-Inducible Protein 16-Mediated Inflammasomes

Singh

Kerur

Bottero

et al. 2013

J Virol

140

146

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“…The telomerase immortalized endothelial cell line (TIVE) latently infected with KSHV (TIVE-LTC), and the PEL derived B-cell line BCBL-1 are well-established in vitro models to study KS and PEL, respectively [2] , [29] . In addition, BJAB-KSHV, a Burkitt's lymphoma B-cell line carrying latent KSHV DNA, has also been used as an additional model for studying KSHV pathogenesis [30] . To test whether the process of glutamate generation is relevant to KS, we measured the secretion of glutamate in KSHV TIVE-LTC cells as well as in uninfected control TIVE cells.…”

Section: Resultsmentioning

confidence: 99%

Glutamate Secretion and Metabotropic Glutamate Receptor 1 Expression during Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Cell Proliferation

et al. 2014

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Kaposi's sarcoma associated herpesvirus (KSHV) is etiologically associated with endothelial Kaposi's sarcoma (KS) and B-cell proliferative primary effusion lymphoma (PEL), common malignancies seen in immunocompromised HIV-1 infected patients. The progression of these cancers occurs by the proliferation of cells latently infected with KSHV, which is highly dependent on autocrine and paracrine factors secreted from the infected cells. Glutamate and glutamate receptors have emerged as key regulators of intracellular signaling pathways and cell proliferation. However, whether they play any role in the pathological changes associated with virus induced oncogenesis is not known. Here, we report the first systematic study of the role of glutamate and its metabotropic glutamate receptor 1 (mGluR1) in KSHV infected cell proliferation. Our studies show increased glutamate secretion and glutaminase expression during de novo KSHV infection of endothelial cells as well as in KSHV latently infected endothelial and B-cells. Increased mGluR1 expression was detected in KSHV infected KS and PEL tissue sections. Increased c-Myc and glutaminase expression in the infected cells was mediated by KSHV latency associated nuclear antigen 1 (LANA-1). In addition, mGluR1 expression regulating host RE-1 silencing transcription factor/neuron restrictive silencer factor (REST/NRSF) was retained in the cytoplasm of infected cells. KSHV latent protein Kaposin A was also involved in the over expression of mGluR1 by interacting with REST in the cytoplasm of infected cells and by regulating the phosphorylation of REST and interaction with β-TRCP for ubiquitination. Colocalization of Kaposin A with REST was also observed in KS and PEL tissue samples. KSHV infected cell proliferation was significantly inhibited by glutamate release inhibitor and mGluR1 antagonists. These studies demonstrated that elevated glutamate secretion and mGluR1 expression play a role in KSHV induced cell proliferation and suggest that targeting glutamate and mGluR1 is an attractive therapeutic strategy to effectively control the KSHV associated malignancies.

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“…Latent KSHV-infected lymphoma cell lines (BC1, BCBL1, and KSHV-BJAB) were cultured in RPMI medium supplemented with 10% fetal bovine serum (FBS) as previously described (44), with the exception that KSHV-BJAB cells were maintained under 0.2-mg/ml hygromycin selection (45). Latent KSHV-infected endothelial L1-TIVE cells (46) were grown in Dulbecco modified Eagle medium (DMEM) supplemented with 100 g/ml streptomycin sulfate and 100 U/ml penicillin G and 5% FBS.…”

Section: Methodsmentioning

confidence: 99%

The Open Chromatin Landscape of Kaposi's Sarcoma-Associated Herpesvirus

Hilton

Simon

Lieb

et al. 2013

J Virol

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Development of a fluorescence-based assay to screen antiviral drugs against Kaposi's sarcoma–associated herpesvirus

Abstract: Tumors associated with Kaposi's sarcoma -associated herpesvirus infection include Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease.

Cited by 14 publications

References 51 publications

Kaposi's Sarcoma-Associated Herpesvirus Latency in Endothelial and B Cells Activates Gamma Interferon-Inducible Protein 16-Mediated Inflammasomes

Kaposi's Sarcoma-Associated Herpesvirus Latency in Endothelial and B Cells Activates Gamma Interferon-Inducible Protein 16-Mediated Inflammasomes

Glutamate Secretion and Metabotropic Glutamate Receptor 1 Expression during Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Cell Proliferation

The Open Chromatin Landscape of Kaposi's Sarcoma-Associated Herpesvirus

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