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Viruses 2011, 3(4), 398-422; doi:10.3390/v3040398

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

Department of Molecular Biology and Biochemistry, Cancer Research Institute, University of California, Irvine, CA 92697, USA
Author to whom correspondence should be addressed.
Received: 16 March 2011 / Accepted: 31 March 2011 / Published: 15 April 2011
(This article belongs to the Special Issue Cell Transformation by RNA Viruses)
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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.
Keywords: retrovirus; proto-oncogene; oncogenesis; retroviral vector; oncogene; non-acute retrovirus; gene therapy retrovirus; proto-oncogene; oncogenesis; retroviral vector; oncogene; non-acute retrovirus; gene therapy
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Fan, H.; Johnson, C. Insertional Oncogenesis by Non-Acute Retroviruses: Implications for Gene Therapy. Viruses 2011, 3, 398-422.

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