Retroviruses and Oncogenes

Rasheed, Suraiya

doi:10.1007/978-1-4899-1721-8_5

Cited by 11 publications

(6 citation statements)

References 576 publications

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“…Historically, much of our knowledge of oncology has been gained by the investigation of acutely transforming retroviruses carrying oncogenes (reviewed in Ref. [18][19][20].…”

Section: Mechanisms Of Retroviral Malignant Cell Transformationmentioning

confidence: 99%

Beneficial and detrimental effects of human endogenous retroviruses

Kurth

Bannert

2009

Intl Journal of Cancer

118

102

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In this mini review, we aim to evaluate the structure and function of Human Endogenous Retroviruses (HERVs) with respect to the benefit they may have for humans or the damage they may cause. Emphasis is laid on their putative roles, if any, in pregnancy, in gene regulation and in cancer. As a basis for this discussion it will first be necessary to briefly describe the structure and function of retroelements, including HERVs, before addressing their positive or negative effects at the cellular and organismal level. Finally, we will give an outlook in which we will attempt to define priorities for future research. The recent sequencing of the entire human genome revealed that almost half consists of transposable elements (TEs), namely DNA transposons (2.8%; 0.3 x 10 6 copies) and the more abundant retroelements (42.2%; 2.7 x 10 6 copies).1,2,3 DNA transposons amplify without RNA intermediates, whereas retroelements (as the name implies) require a reverse transcriptase to retrotranscribe RNA into DNA copies that will subsequently integrate into chromosomal DNA. TEs have often been regarded as ''selfish DNA'' or ''junk DNA,'' but it remains unclear whether they are really all ''junk,'' because upon becoming part of our genome, like all genes they are subject to natural selection and can be co-opted for the benefit of the host. Indeed, it may well turn out that TEs, in addition to other already measurable positive effects (some of which are described below), may play a major role in shaping our genome by increasing its plasticity and in the evolution of mammalian gene regulation networks.4-7 HERVs belong to the retroelements, which can be subdivided into those with regulatory long terminal repeats (LTRs, 8.3% of our DNA; 0.3 x 10 6 copies) and retroelements without LTRs (33.9%; 2.4 x 10 6 copies) (Fig. 1). Among the non-LTR members, short and long interspersed elements (SINEs and LINEs, respectively) are present in very high copy numbers. SINEs cannot code for proteins whereas LINEs encode a reverse transcriptase (RT) that can be utilized by both SINEs and LINEs for retrotranspositions or for the formation of pseudogenes. It is unknown whether the LINE RT can also be used by additional retroelements like HERVs for retrotransposition. The LTR containing retroelements can be grouped into 6 superfamilies.8 Class I-III HERVs possess limited nucleotide sequence homologies to C-, B-or spumaretroviruses, respectively. The other superfamilies MER4, MST and MLT represent ancient retrotransposons not known to be still functional in humans today. Basic Genomic Organization and Replication of HERVs To discuss the functions of HERVs that make up 8% of the human genome, one needs to look at their genetic organization. 1,9 All exogenous and preserved endogenous retrovirus strains have the basic genetic order 50-gag-pro-pol-env-30. Gag codes for matrix and capsid proteins, pro for protease, pol for reverse transcriptase, RNase H and integrase and env for envelope, as illustrated in Figure 2 for the youngest and most active human endo...

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“…Historically, much of our knowledge of oncology has been gained by the investigation of acutely transforming retroviruses carrying oncogenes (reviewed in Ref. [18][19][20].…”

Section: Mechanisms Of Retroviral Malignant Cell Transformationmentioning

confidence: 99%

Beneficial and detrimental effects of human endogenous retroviruses

Kurth

Bannert

2009

Intl Journal of Cancer

118

102

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“…The major mechanism of ALV pathogenesis is that of typical oncogene activation by proviral insertion gene deregulation, resulting in tumour formation after chronic infection. Acute-transforming ALV variants have been discovered that have acquired an activated oncogene in their genome and these cause tumours in a short period of time (Graf & Beug, 1978; Hayward et al , 1981; Rasheed, 1995; Gong et al , 1998; Yang et al , 2007).…”

Section: Introductionmentioning

confidence: 99%

The PI3K/Akt pathway is involved in early infection of some exogenous avian leukosis viruses

Feng

Cao

Liao

2011

Journal of General Virology

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Avian leukosis virus (ALV) is an enveloped and oncogenic retrovirus. Avian leukosis caused by the members of ALV subgroups A, B and J has become one of the major problems challenging the poultry industry in China. However, the cellular factors such as signal transduction pathways involved in ALV infection are not well defined. In this study, our data demonstrated that ALV-J strain NX0101 infection in primary chicken embryo fibroblasts or DF-1 cells was correlated with the activity and phosphorylation of Akt. Akt activation was initiated at a very early stage of infection independently of NX0101 replication. The specific phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 or wortmannin could suppress Akt phosphorylation, indicating that NX0101-induced Akt phosphorylation is PI3K-dependent. ALV-A strain GD08 or ALV-B strain CD08 infection also demonstrated a similar profile of PI3K/Akt activation. Treatment of DF-1 cells with the drug 5-(N, N-hexamethylene) amiloride that inhibits the activity of chicken Na + /H + exchanger type 1 significantly reduced Akt activation induced by NX0101, but not by GD08 and CD08. Akt activation triggered by GD08 or CD08 was abolished by clathrin-mediated endocytosis inhibitor chlorpromazine. Receptor-mediated endocytosis inhibitor dansylcadaverine had a negligible effect on all ALV-induced Akt phosphorylation. Moreover, viral replication of ALV was suppressed by LY294002 in a dose-dependent manner, which was due to the inhibition of virus infection by LY294002. These data suggest that the activation of the PI3K/Akt signalling pathway by exogenous ALV infection plays an important role in viral entry, yet the precise mechanism remains under further investigation. INTRODUCTIONAvian leukosis virus (ALV) is an oncogenic retrovirus that primarily infects chickens. Based on the identity of the surface region (SU) of its envelope glycoprotein, ALV is divided into different subgroups, designated A through to F and J (Coffin et al., 1997). ALV-E is endogenous virus, while all other subgroups are exogenous. Recently, the disease caused by ALV-J, ALV-A or ALV-B has become one of the major problems facing the poultry industry in China, which has been identified in the commercial meat and eggtype chickens, and also in the Chinese local breeds (Du et al., 2000;Cui et al., 2003;Cheng et al., 2010;Zhang et al., 2010). ALV can induce a rather wide variety of tumours and mortality that cause significant economic losses. The various pathotypes of tumours are mainly lymphomas, myelocytomas and haemangiomas, as well as fibrosarcomas, histiocytic sarcomas, intestinal adenocarcinoma, leiomyosarcoma and so on (Xu et al., 2004;Sun & Cui, 2007;Cheng et al., 2010). The major mechanism of ALV pathogenesis is that of typical oncogene activation by proviral insertion gene deregulation, resulting in tumour formation after chronic infection. Acute-transforming ALV variants have been discovered that have acquired an activated oncogene in their genome and these cause tumours in a short period of time (Graf & Beu...

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“…After 2 weeks, we isolated 12 HAT-resistant clones. We reasoned that if overexpression of a particular cDNA caused the HAT-resistant phenotype, then we could rescue the cDNA sequence by packaging of the retroviral RNA by the Gag, Pol, and Env proteins derived from superinfecting wild-type Moloney retroviruses (Rasheed 1995). The rescued retrovirus transducing the cDNA should allow transfer of the HAT-resistant phenotype to fresh BAH-ER3 cells.…”

Section: Isolation Of Cell Clones With Constitutive Tgf-␤ Signaling Omentioning

confidence: 99%

Synergistic cooperation of TFE3 and Smad proteins in TGF-β-induced transcription of the plasminogen activator inhibitor-1 gene

Hua¹,

Liu²,

Ansari³

et al. 1998

Genes Dev.

271

249

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Members of the TGF-␤ superfamily influence a broad range of biological activities including stimulation of wound healing and inhibition of cell growth. TGF-␤ signals through type I and II receptor serine/ threonine kinases and induces transcription of many genes including plasminogen activator inhibitor-1 (PAI-1). To identify proteins that participate in TGF-␤-induced gene expression, we developed a novel retrovirus-mediated expression cloning strategy; and using this approach, we established that transcription factor µE3 (TFE3) is involved in TGF-␤-induced activation of the PAI-1 promoter. We showed that TFE3 binds to an E-box sequence in PE2, a 56-bp promoter fragment of the PAI-1 promoter, and that mutation of this sequence abolishes both TFE3 binding as well as TGF-␤-dependent activation. TFE3 and Smad3 synergistically activate the PE2 promoter and phosphorylated Smad3 and Smad4 bind to a sequence adjacent to the TFE3-binding site in this promoter. Binding of both TFE3 and the Smad proteins to their cognate sequences is indispensable for TGF-␤-inducible activation of the PE2 promoter. Hence, TFE3 is an important transcription factor in at least one TGF-␤-activated signal transduction pathway.

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Retroviruses and Oncogenes

Cited by 11 publications

References 576 publications

Beneficial and detrimental effects of human endogenous retroviruses

Beneficial and detrimental effects of human endogenous retroviruses

The PI3K/Akt pathway is involved in early infection of some exogenous avian leukosis viruses

Synergistic cooperation of TFE3 and Smad proteins in TGF-β-induced transcription of the plasminogen activator inhibitor-1 gene

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