Detection of EBV, HBV, HCV, HIV-1, HTLV-I and -II, and SMRV in Human and Other Primate Cell Lines

Uphoff, Cord C.; Denkmann, Sabine A.; Steube, Klaus G.; Drexler, Hans G.

doi:10.1155/2010/904767

Cited by 41 publications

(35 citation statements)

References 45 publications

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“…The DOHH-2 cell line was originally categorized as EBV negative (16) and a cell line vendor, Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ), classifies it as EBV negative. Nevertheless, a previous study showed the presence of EBV in DOHH-2 cells by PCR analysis with EBV episomes detected in only a small fraction of cells by FISH (17). Since the DOHH-2 cell line was derived by the clonal expansion of a mixed EBV negative and EBV positive culture as described by DSMZ, it is possible that there was carryover of a small percentage of EBV positive cells during the selection of EBV negative cells.…”

Section: Resultsmentioning

confidence: 99%

High-Throughput RNA Sequencing-Based Virome Analysis of 50 Lymphoma Cell Lines from the Cancer Cell Line Encyclopedia Project

Cao¹,

Strong²,

Wang³

et al. 2015

J Virol

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Using high-throughput RNA sequencing data from 50 common lymphoma cell culture models from the Cancer Cell Line Encyclopedia project, we performed an unbiased global interrogation for the presence of a panel of 740 viruses and strains known to infect human and other mammalian cells. This led to the findings of previously identified infections by Epstein-Barr virus (EBV), Kaposi's sarcoma herpesvirus (KSHV), and human T-lymphotropic virus type 1 (HTLV-1). In addition, we also found a previously unreported infection of one cell line (DEL) with a murine leukemia virus. High expression of murine leukemia virus (MuLV) transcripts was observed in DEL cells, and we identified four transcriptionally active integration sites, one being in the TNFRSF6B gene. We also found low levels of MuLV reads in a number of other cell lines and provided evidence suggesting crosscontamination during sequencing. Analysis of HTLV-1 integrations in two cell lines, HuT 102 and MJ, identified 14 and 66 transcriptionally active integration sites with potentially activating integrations in immune regulatory genes, including interleukin-15 (IL-15), IL-6ST, STAT5B, HIVEP1, and IL-9R. Although KSHV and EBV do not typically integrate into the genome, we investigated a previously identified integration of EBV into the BACH2 locus in Raji cells. This analysis identified a BACH2 disruption mechanism involving splice donor sequestration. Through viral gene expression analysis, we detected expression of stable intronic RNAs from the EBV BamHI W repeats that may be part of long transcripts spanning the repeat region. We also observed transcripts at the EBV vIL-10 locus exclusively in the Hodgkin's lymphoma cell line, Hs 611.T, the expression of which were uncoupled from other lytic genes. Assessment of the KSHV viral transcriptome in BCP-1 cells showed expression of the viral immune regulators, K2/vIL-6, K4/vIL-8-like vCCL1, and K5/E2-ubiquitin ligase 1 that was significantly higher than expression of the latency-associated nuclear antigen. Together, this investigation sheds light into the virus composition across these lymphoma model systems and provides insights into common viral mechanistic principles. IMPORTANCEViruses cause cancer in humans. In lymphomas the Epstein-Barr virus (EBV), Kaposi's sarcoma herpesvirus (KSHV) and human T-lymphotropic virus type 1 are major contributors to oncogenesis. We assessed virus-host interactions using a high throughput sequencing method that facilitates the discovery of new virus-host associations and the investigation into how the viruses alter their host environment. We found a previously unknown murine leukemia virus infection in one cell line. We identified cellular genes, including cytokine regulators, that are disrupted by virus integration, and we determined mechanisms through which virus integration causes deregulation of cellular gene expression. Investigation into the KSHV transcriptome in the BCP-1 cell line revealed high-level expression of immune signaling genes. EBV transcriptome analysis sh...

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Section: Resultsmentioning

confidence: 99%

High-Throughput RNA Sequencing-Based Virome Analysis of 50 Lymphoma Cell Lines from the Cancer Cell Line Encyclopedia Project

Cao¹,

Strong²,

Wang³

et al. 2015

J Virol

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“…Detection of EBV, HBV, HCV, HIV-1, HIV-2, HTLV-I/II, MLV, and SMRV was carried out as described previously (Uphoff et al 2010(Uphoff et al , 2015.…”

Section: Analyses Of Mycoplasma and Viral Contaminationsmentioning

confidence: 99%

Differential Requirements for the RAD51 Paralogs in Genome Repair and Maintenance in Human Cells

Garcin

Gon

Prakash

et al. 2019

Preprint

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Deficiency in several of the classical human RAD51 paralogs [RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3] is associated with cancer predisposition and Fanconi anemia. To investigate their functions, isogenic disruption mutants for each were generated in non-transformed MCF10A mammary epithelial cells and in transformed U2OS and HEK293 cells. In U2OS and HEK293 cells, viable ablated clones were readily isolated for each RAD51 paralog; in contrast, with the exception of RAD51B, RAD51 paralogs are cell-essential in MCF10A cells. Underlining their importance for genomic stability, mutant cell lines display variable growth defects, impaired sister chromatid recombination, reduced levels of stable RAD51 nuclear foci, and hypersensitivity to mitomycin C and olaparib. Altogether these observations underscore the contributions of RAD51 paralogs in diverse DNA repair processes, and demonstrate essential differences in different cell types. Finally, this study will provide useful reagents to analyze patient-derived mutations and to investigate mechanisms of chemotherapeutic resistance deployed by cancers.

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“…NK-92 is an established and well-characterized homogeneous cell line that has been successfully reproduced and expanded using good manufacturing practice (GMP)-compliant cryopreserved master cell banks. 110 It is a continuously expanding line and "limitless" in number, allowing the 119 While most groups agree that 1,000 cGy of radiation is sufficient to prevent engraftment of NK-92 cells with minimal effect on their in vitro cytotoxicity, irradiation prior to infusion is likely to negatively impact their in vivo proliferation, persistence, and long-term antitumor efficacy. 100 The efficacy of CAR-T cells is accepted to be dependent on persistence, 4,67 and similarly, the in vivo efficacy of adoptively infused NK cells has been shown to depend on their in vivo expansion and persistence.…”

Section: Studies With Car-modified Nk Cell Linesmentioning

confidence: 99%

Engineering Natural Killer Cells for Cancer Immunotherapy

et al. 2017

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The past several years have seen tremendous advances in the engineering of immune effector cells as therapy for cancer. While chimeric antigen receptors (CARs) have been used extensively to redirect the specificity of autologous T cells against hematological malignancies with striking clinical results, studies of CAR-modified natural killer (NK) cells have been largely preclinical. In this review, we focus on recent advances in NK cell engineering, particularly on preclinical evidence suggesting that NK cells may be as effective as T cells in recognizing and killing targets after genetic modification. We will discuss strategies to introduce CARs into both primary NK cells and NK cell lines in an effort to provide antigen specificity, the challenges of manufacturing engineered NK cells, and evidence supporting the effectiveness of this approach from preclinical and early-phase clinical studies using CAR-engineered NK cells. CAR-NK cells hold great promise as a novel cellular immunotherapy against refractory malignancies. Notably, NK cells can provide an "off-the-shelf" product, eliminating the need for a personalized and patient-specific product that plagues current CAR-T cell therapies. The ability to more potently direct NK cell-mediated cytotoxicity against refractory tumors through the expression of CAR is likely to contribute to the recent paradigm shift in cancer treatment.

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Detection of EBV, HBV, HCV, HIV-1, HTLV-I and -II, and SMRV in Human and Other Primate Cell Lines

Cited by 41 publications

References 45 publications

High-Throughput RNA Sequencing-Based Virome Analysis of 50 Lymphoma Cell Lines from the Cancer Cell Line Encyclopedia Project

High-Throughput RNA Sequencing-Based Virome Analysis of 50 Lymphoma Cell Lines from the Cancer Cell Line Encyclopedia Project

Differential Requirements for the RAD51 Paralogs in Genome Repair and Maintenance in Human Cells

Engineering Natural Killer Cells for Cancer Immunotherapy

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