Retroviruses and Their Role in Cancer

Fan, Hung

doi:10.1007/978-1-4899-1730-0_7

Cited by 32 publications

(25 citation statements)

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“…The LTR retrotransposons have been suggested to be selfish DNAs that do not serve relevant host functions (8). However, recent findings indicate that the solo LTRs can provide enhancers and promoters for cis-linked genes and regulate host gene transcription (9,10,22,25,26,29).The human genome contains approximately 50 copies of the ERV-9 endogenous retrovirus and an additional 3,000 to 4,000 copies of solitary ERV-9 LTRs (15,17,19,35,36). Compared with the LTRs of other families of endogenous retroviruses, the ERV-9 LTRs exhibit an unusual sequence feature: the U3 regions contain from 5 to 17 tandem repeats of 37 to 41 bases (17, 18) with recurrent GATA (23), CCAAT (28), and CCACC (21) motifs potentially capable of binding to cognate transcription factors expressed in embryonic and hematopoietic cells.…”

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The Solitary Long Terminal Repeats of ERV-9 Endogenous Retrovirus Are Conserved during Primate Evolution and Possess Enhancer Activities in Embryonic and Hematopoietic Cells

Ling¹,

Pi²,

Bollag

et al. 2002

J Virol

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The solitary long terminal repeats (LTRs) of ERV-9 endogenous retrovirus contain the U3, R, and U5 regions but no internal viral genes. They are middle repetitive DNAs present at 2,000 to 4,000 copies in primate genomes. Sequence analyses of the 5 boundary area of the erythroid ␤-globin locus control region (␤-LCR) and the intron of the embryonic axin gene show that a solitary ERV-9 LTR has been stably integrated in the respective loci for at least 15 million years in the higher primates from orangutan to human. The solitary long terminal repeats (LTRs) of human endogenous retroviruses comprise approximately 5% of the human genome and belong to the category of middle repetitive DNAs characterized as retrotransposons (14,19,24,35). These solitary LTRs contain the U3 enhancer and promoter region, the transcribed R region whose 5Ј end marks the initiation site of retroviral RNA synthesis, and the U5 region (27) but no internal gag, pol, and env genes. During primate evolution, the LTRs were apparently self-replicated and inserted into various host chromosomal sites. The functional roles in the host genomes of these transposed, repetitive DNAs are not clear. The LTR retrotransposons have been suggested to be selfish DNAs that do not serve relevant host functions (8). However, recent findings indicate that the solo LTRs can provide enhancers and promoters for cis-linked genes and regulate host gene transcription (9,10,22,25,26,29).The human genome contains approximately 50 copies of the ERV-9 endogenous retrovirus and an additional 3,000 to 4,000 copies of solitary ERV-9 LTRs (15,17,19,35,36). Compared with the LTRs of other families of endogenous retroviruses, the ERV-9 LTRs exhibit an unusual sequence feature: the U3 regions contain from 5 to 17 tandem repeats of 37 to 41 bases (17, 18) with recurrent GATA (23), CCAAT (28), and CCACC (21) motifs potentially capable of binding to cognate transcription factors expressed in embryonic and hematopoietic cells.This suggests that the ERV-9 enhancer and promoter could be active in those cells.To gain further insight into the stability and functional significance of the ERV-9 LTRs, here we have mapped the erythroid ␤-globin and embryonic axin gene loci in primates by using human primers in PCR. We found a solitary ERV-9 LTR that is conserved in identical locations in the 5Ј boundary area of the ␤-globin gene locus and in the axin gene in the higher primates orangutan, gorilla, chimpanzee, and human, whose ancestors diverged over an evolutionary period of 15 million years (12). In the lower primates gibbon and monkey, whose ancestors diverged from the human ancestor 18 and 25 million years ago, respectively (12), the globin and axin LTRs are absent in the respective gene loci. However, other ERV-9 LTRs are detectable in the monkey genome. These results indicate that copies of the ERV-9 LTRs present in the lower primates were inserted into the globin and axin gene loci in the common ancestor of the higher primates 15 to 18 millions years ago and have remained stably integrate...

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The Solitary Long Terminal Repeats of ERV-9 Endogenous Retrovirus Are Conserved during Primate Evolution and Possess Enhancer Activities in Embryonic and Hematopoietic Cells

Ling¹,

Pi²,

Bollag

et al. 2002

J Virol

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“…Retroviruses alter cell proliferation through the capture and deregulated expression of cellular proto-oncogenes, integration near or within the coding or regulatory regions of proto-oncogenes, or production of oncogenic viral gene products (10). In lower vertebrates, the role of retroviruses in tumor diseases has been established primarily through electron microscopic observations and detection of reverse transcriptase (RT) activity (12).…”

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Identification and Characterization of an Exogenous Retrovirus from Atlantic Salmon Swim Bladder Sarcomas

Paul

Quackenbush

Sutton

et al. 2006

J Virol

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A novel piscine retrovirus has been identified in association with an outbreak of leiomyosarcoma in the swim bladders of Atlantic salmon. The complete nucleotide sequence of the Atlantic salmon swim bladder sarcoma virus (SSSV) provirus is 10.9 kb in length and shares a structure and transcriptional profile similar to those of murine leukemia virus-like simple retroviruses. SSSV appears unique to simple retroviruses by not harboring sequences in the Atlantic salmon genome. Additionally, SSSV differs from other retroviruses in potentially utilizing a methionine tRNA primer binding site. SSSV-associated tumors contain high proviral copy numbers (greater than 30 per cell) and a polyclonal integration pattern. Phylogenetic analysis based on reverse transcriptase places SSSV with zebrafish endogenous retrovirus (ZFERV) between the Gammaretrovirus and Epsilonretrovirus genera. Large regions of continuous homology between SSSV and ZFERV Gag, Pol, and Env suggest that these viruses represent a new group of related piscine retroviruses.

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“…A wide variety of oncogenic viruses have been identified in mammals and birds, primarily from the Retroviridae family and from 5 families of DNA viruses: Polyomaviruses, Papillomaviruses, Adenoviruses, Herpesviruses and Hepadnaviruses (Tooze 1980, Fan 1994. These viruses have been indispensable for experimental manipulations of tumorigenesis in a variety of cell types.…”

Section: Introductionmentioning

confidence: 99%

“…The majority of tumors caused by DNA viruses and retroviruses are papillomas, sarcomas, lymphomas and leukemias (Fan 1994). No transmissible tumors have been identified which involve cells derived from the embryonic neural crest, including neurons, Schwann cells, other glial cell types or melanophores.…”

Section: Introductionmentioning

confidence: 99%

A virus-like agent associated with neurofibromatosis in damselfish

Schmale¹,

Gibbs²,

Campbell³

2002

Dis. Aquat. Org.

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Damselfish neurofibromatosis (DNF) is a transmissible disease involving neurofibromas and chromatophoromas affecting bicolor damselfish Stegastes partitus on Florida reefs. Analysis of genomic DNA by Southern blotting techniques demonstrated the presence of a group of extrachromosomal DNAs in tumors from fish affected with DNF but not in healthy individuals. Cell lines obtained from tumors contained identical DNAs and were shown to be tumorigenic in vivo, while lines established from healthy fish did not contain such DNA and were not tumorigenic. These DNA patterns were also observed in experimentally induced tumors. A DNase resistant component of this DNA was isolated from both tumor cells and conditioned media of tumor cell lines suggesting that these sequences were encapsulated in viral particles. These data support the hypothesis that one or more of these extrachromosomal DNA forms is the genome of an unusual virus and that this virus is the etiologic agent of DNF. We have tentatively termed this agent the damselfish virus-like agent (DVLA).KEY WORDS: Neurofibroma · Damselfish · Tumor · Virus · Schwann Cell · Chromatophore Resale or republication not permitted without written consent of the publisherDis Aquat Org 49: [107][108][109][110][111][112][113][114][115] 2002 lines maintained in culture for many years, indicating that DNF is caused by a sub-cellular infectious agent (Schmale 1995). We have previously demonstrated the presence of several retroviruses in damselfish cell lines (Schmale et al. 1996 and unpubl. data). However, retroviral genomes could not be detected consistently in damselfish tumors or other tissues and thus cannot be considered a likely etiologic agent of this disease.In this study we report the occurrence of a group of extrachromosomal DNAs (eDNA) in tumors from fish affected with DNF but not in healthy individuals. We have determined the distribution of this eDNA in both tumor bearing and healthy fish, and cell lines derived from such fish, and conducted in vivo transmission studies to investigate the relationship of these DNAs to tumorigenesis. We have also assessed resistance to DNase treatment as an indicator of possible encapsulation of this eDNA into intra-or extracellular particles. MATERIALS AND METHODSDamselfish and cell cultures. Bicolor damselfish Stegastes (previously Pomacentrus) partitus were collected on reefs in South Florida which had previously been surveyed to determine disease prevalence rates (Schmale 1991). Healthy fish used for experimental tumor induction were collected from a single low disease prevalence reef, Fowey Rocks. Fish were maintained in either recirculating or flow-through marine aquaria of ≥ 35 l at 20-30°C. Normal fish were observed in the laboratory for several weeks following capture to confirm initial observations that they lacked any signs of DNF. DNF was identified by visual inspection for external tumors as described in Schmale et al. (1986). Spontaneous tumors were obtained from fish with DNF collected in the wild. Fish were eut...

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Retroviruses and Their Role in Cancer

Cited by 32 publications

References 263 publications

The Solitary Long Terminal Repeats of ERV-9 Endogenous Retrovirus Are Conserved during Primate Evolution and Possess Enhancer Activities in Embryonic and Hematopoietic Cells

The Solitary Long Terminal Repeats of ERV-9 Endogenous Retrovirus Are Conserved during Primate Evolution and Possess Enhancer Activities in Embryonic and Hematopoietic Cells

Identification and Characterization of an Exogenous Retrovirus from Atlantic Salmon Swim Bladder Sarcomas

A virus-like agent associated with neurofibromatosis in damselfish

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