Department of Molecular Biology and Biochemistry, Cancer Research Institute, University of California, Irvine, CA 92697, USA.
Viruses. 2011 Apr;3(4):398-422. doi: 10.3390/v3040398. Epub 2011 Apr 15.
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.
逆转录病毒在多种动物和人类中引起癌症。对逆转录病毒的研究为人类致癌机制提供了重要的见解，包括发现病毒癌基因和细胞原癌基因。本综述的主题是不携带癌基因的逆转录病毒（非急性逆转录病毒）引起癌症的机制。共同的主题是，这些肿瘤是由于病毒 DNA 整合导致细胞原癌基因的插入激活引起的。回顾了早期关于病毒诱导肿瘤中原癌基因插入激活的研究。对非急性逆转录病毒的研究通过搜索病毒诱导肿瘤中的常见插入位点（CIS），发现了新的原癌基因。通过研究逆转录病毒诱导的肿瘤阐明了不同原癌基因在肿瘤发展中的合作，通过遗传易感小鼠的逆转录病毒感染（逆转录病毒标记），鉴定了在特定致癌途径中活跃的细胞原癌基因。包括病毒整合位点的 PCR 克隆、小鼠基因组序列的可用性和高通量 DNA 测序在内的技术进步，加速了原癌基因的发现。在使用逆转录病毒载体纠正遗传缺陷的基因治疗试验中，插入激活已被证明是一个重大风险。非急性逆转录病毒致癌研究为潜在风险和致癌机制提供了深入了解。
