Insertional Oncogenesis by Non-Acute Retroviruses: Implications for Gene Therapy

被引：34

作者：

Fan, Hung ^{[1
]}

Johnson, Chassidy ^{[1
]}

机构：

[1] Univ Calif Irvine, Dept Mol Biol & Biochem, Canc Res Inst, Irvine, CA 92697 USA

来源：

VIRUSES-BASEL | 2011年 / 3卷 / 04期

关键词：

retrovirus; proto-oncogene; oncogenesis; retroviral vector; oncogene; non-acute retrovirus; gene therapy; MURINE LEUKEMIA-VIRUS; MAMMARY-TUMOR VIRUS; T-CELL LYMPHOMAS; SEVERE COMBINED IMMUNODEFICIENCY; MYC TRANSGENIC MICE; ROUS-SARCOMA VIRUS; C-ERBB ACTIVATION; INDUCED ERYTHROBLASTOSIS; INFECTIOUS RETROVIRUS; PROVIRUS INTEGRATION;

D O I：

10.3390/v3040398

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Retroviruses cause cancers in a variety of animals and humans. Research on retroviruses has provided important insights into mechanisms of oncogenesis in humans, including the discovery of viral oncogenes and cellular proto-oncogenes. The subject of this review is the mechanisms by which retroviruses that do not carry oncogenes (non-acute retroviruses) cause cancers. The common theme is that these tumors result from insertional activation of cellular proto-oncogenes by integration of viral DNA. Early research on insertional activation of proto-oncogenes in virus-induced tumors is reviewed. Research on non-acute retroviruses has led to the discovery of new proto-oncogenes through searches for common insertion sites (CISs) in virus-induced tumors. Cooperation between different proto-oncogenes in development of tumors has been elucidated through the study of retrovirus-induced tumors, and retroviral infection of genetically susceptible mice (retroviral tagging) has been used to identify cellular proto-oncogenes active in specific oncogenic pathways. The pace of proto-oncogene discovery has been accelerated by technical advances including PCR cloning of viral integration sites, the availability of the mouse genome sequence, and high throughput DNA sequencing. Insertional activation has proven to be a significant risk in gene therapy trials to correct genetic defects with retroviral vectors. Studies on non-acute retroviral oncogenesis provide insight into the potential risks, and the mechanisms of oncogenesis.

引用

页码：398 / 422

页数：25

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