Cloning of the MCF1233 murine leukemia virus and identification of sequences involved in viral tropism, oncogenicity and T cell epitope formation

Sijts, Alice J.A.M.; Leupers, C. J. M.; Mengede, E. A. M.; Loenen, W. A. M.; Elsen, Peter J. van den; Melief, C. J. M.

doi:10.1016/0168-1702(94)90133-3

Cited by 19 publications

(11 citation statements)

References 34 publications

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“…32 Differences between B and N-tropic retroviruses are known to be located in the p30 Gag region, 22,23 and indeed, sequence alignment of MelARV and Emv-2 revealed 2 divergent regions of limited extent, one located in the pol region (nt 3,160-3,575) and the other in the p30 gag domain (nt 1,360-1,726) with the latter being the characteristic signatures for B-tropic and N-tropic retroviruses, respectively. In silico homology searches performed using the MelARV-specific gag region identified a provirus located in the qA3 region of chromosome 5 of C57BL/6 mice (as well as a sequence from the oncogenic infectious Mink Cell Focus-inducing virus 1233 MLV 33 ). Sequence alignments of MelARV with the endogenous Emv-2 and Chr5 proviruses strongly suggest that the Emv-2 provirus has provided the ecotropic backbone of MelARV, sharing with it more than 99.8% nucleotide sequence identity except for the gag B-tropic region (nt 1,360-1,726) and a small pol region (nt 3,160-3,575) that have been provided by the Chr5 endogenous provirus.…”

Section: Discussionmentioning

confidence: 99%

Mobility and integration sites of a murine C57BL/6 melanoma endogenous retrovirus involved in tumor progression in vivo

Pothlichet

Mangeney

Heidmann

2006

Intl Journal of Cancer

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Tumor development is a multistep process in which both genetic and epigenetic events cooperate for the emergence of a malignant clone with metastatic properties. The possibility that endogenous retroviruses promote the expansion of a neoplastic clone by subverting immunosurveillance has been proposed and recently demonstrated in the case of the B16 murine melanoma, which spontaneously express the melanoma-associated retrovirus (MelARV). Indeed, knocking down, by RNA interference, this endogenous retrovirus resulted in the rejection of the tumor cells in immunocompetent mice, without any alteration of their transformed phenotype. Here, we characterize the MelARV proviruses present in the B16 melanoma. Complete sequencing of the viral genomic RNA and characterization of the integration sites within both the B16 tumor cells and a subline selected in vivo for increased metastatic activity disclosed mobility of the element with new proviral insertions targeting critical genes and altering their transcriptional profile. The results show that MelARV can act both at the genetic level, inducing mutations by insertion, and at the epigenetic level, promoting immunosuppression of the host. These properties may as well be relevant to human tumors, such as germline tumors and melanoma, where endogenous retroviruses are active. ' 2006 Wiley-Liss, Inc.Key words: endogenous retrovirus; murine melanoma; insertional mutagenesis; metastasis Most cancer deaths result from the invasion of surrounding tissues by tumor cells and widespread metastasis to vital organs. The generation of metastatic tumor cells is a multistep process, which involves a series of genetic alterations, including cell transformation via mutations of oncogenes and/or tumor suppressor genes, inhibition of the host immune response and acquisition of an invasive potential. Tumors can be triggered by infectious oncogenic retroviruses that are able to perform at least some of the abovementioned steps, most often via insertional mutagenesis. [1][2][3] This is for instance the case of a series of slow transforming murine retroviruses such as the Moloney murine leukemia virus, which only possesses the 3 canonical gag, pol and env genes but no transduced oncogene and yet induces leukemia by integrating close to critical cellular genes that are consequently deregulated. Interestingly, all mammalian genomes contain endogenous retroviruses (ERVs) that are the genomic traces of ancestral infections of the germline by active retroviruses. [4][5][6] Most of these elements are defective, but some of them have retained intact open reading frames (ORFs). These elements are normally silent but several of them are found to be transcriptionally activated in some tumors, as revealed by the occurrence of viral-like particles. 7,8 Indeed, in the B16 spontaneous melanoma of C57BL/6 mice, an ecotropic ERV-the melanoma-associated retrovirus (MelARV)-is induced, and has been demonstrated to be involved in tumorigenesis. 9,10 Mangeney et al. 10 have recently shown that MelARV expression is...

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Section: Discussionmentioning

confidence: 99%

Mobility and integration sites of a murine C57BL/6 melanoma endogenous retrovirus involved in tumor progression in vivo

Pothlichet

Mangeney

Heidmann

2006

Intl Journal of Cancer

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“…Messenger RNA from mouse tissues was extracted as described above and subjected to cDNA synthesis using the First-strand cDNA Synthesis kit (Amersham Pharmacia Biotech.). Then 2 l of cDNA was used for PCR amplification in the presence of specific primer pairs (ODEG0-17: 5Ј-AGCAGCCTGGTGACAAAATG-3Ј and 5Ј-CTAACCACCTGGAATGCTGG-3Ј, MOGP: 5Ј-ACAGTGATGGTA-CTGCCTAC-3Ј and 5Ј-ATATGACTGAGTCAATAAAC-3Ј, GAPDH: 5Ј-ACCACAGTCCATGCCATCAC-3Ј and 5Ј-TCCACCACCCTGT-TGCTGTA-3Ј) as described (27). The PCR cycles are 94°C for 5 min, then 23 (for GAPDH) or 28 (for ODEG0-17 and MOGP) cycles of 94°C for 30 s, 57°C for 30 s, and 72°C for 1 min, and a final extension at 72°C for 5 min.…”

Section: Suppression Subtractive Hybridization (Ssh)mentioning

confidence: 99%

Suppression Subtractive Hybridization Identifies Genes Expressed in Oviduct during Mouse Preimplantation Period

Lee

Kwok

Yeung

2000

Biochemical and Biophysical Research Communications

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“…1C), we further explored the presence of MuLV in the JY RNA-seq data. Novoalign indices were built for the genomes of three MuLV strains (NCBI accession numbers AF221065 [15], HQ246218, and U13766 [17]) and one strain of the MuLV relative xenotropic murine leukemia virus-related virus (XMRV) (NCBI accession number DQ399707 [23]). The JY RNA-seq data were then aligned to each of these genomes using Novoalign.…”

Section: Detection Of Mulv In Jy Cells Using Parsesmentioning

confidence: 99%

Detection of Murine Leukemia Virus in the Epstein-Barr Virus-Positive Human B-Cell Line JY, Using a Computational RNA-Seq-Based Exogenous Agent Detection Pipeline, PARSES

Lin

Puetter

Coco

et al. 2012

J Virol

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bMany cell lines commonly used for biological studies have been found to harbor exogenous agents such as the human tumor viruses Epstein-Barr virus (EBV) and human papillomavirus. Nevertheless, broad-based, unbiased approaches to globally assess the presence of ectopic organisms within cell model systems have not previously been available. We reasoned that highthroughput sequencing should provide unparalleled insights into the microbiomes of tissue culture cell systems. Here we have used our RNA-seq analysis pipeline, PARSES (Pipeline for Analysis of RNA-Seq Exogenous Sequences), to investigate the presence of ectopic organisms within two EBV-positive B-cell lines commonly used by EBV researchers. Sequencing data sets from both the Akata and JY B-cell lines were found to contain reads for EBV, and the JY data set was found to also contain reads from the murine leukemia virus (MuLV). Further investigation revealed that MuLV transcription in JY cells is highly active. We also identified a number of MuLV alternative splicing events, and we uncovered evidence of APOBEC3G (apolipoprotein B mRNAediting enzyme, catalytic polypeptide-like 3G)-dependent DNA editing. Finally, reverse transcription-PCR analysis showed the presence of MuLV in three other human B-cell lines (DG75, Ramos, and P3HR1 Cl.13) commonly used by investigators in the Epstein-Barr virus field. We believe that a thorough examination of tissue culture microbiomes using RNA-seq/PARSES-like approaches is critical for the appropriate utilization of these systems in biological studies.

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Cloning of the MCF1233 murine leukemia virus and identification of sequences involved in viral tropism, oncogenicity and T cell epitope formation

Cited by 19 publications

References 34 publications

Mobility and integration sites of a murine C57BL/6 melanoma endogenous retrovirus involved in tumor progression in vivo

Mobility and integration sites of a murine C57BL/6 melanoma endogenous retrovirus involved in tumor progression in vivo

Suppression Subtractive Hybridization Identifies Genes Expressed in Oviduct during Mouse Preimplantation Period

Detection of Murine Leukemia Virus in the Epstein-Barr Virus-Positive Human B-Cell Line JY, Using a Computational RNA-Seq-Based Exogenous Agent Detection Pipeline, PARSES

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