Muriaux Delphine, Rein Alan
HIV Drug Resistance Program, National Cancer Institute-Frederick, P.O. Box B, Frederick, MD 21702-1201, USA.
Front Biosci. 2003 Jan 1;8:d135-42. doi: 10.2741/950.
Retroviruses normally package their genomic RNA with high fidelity. However, the fidelity is apparently imperfect, since some cellular mRNA is present in standard retrovirus particles. Further, transcripts originating in the 5' LTR of the integrated provirus sometimes extend beyond the 3' end of the provirus, resulting in the production of chimeric RNAs containing both viral and cellular sequences. These RNAs can be exported to the cytoplasm and packaged into assembling virus particles. When such particles infect a new host cell, reverse transcriptase may copy the cellular sequences, as well as viral sequences, into DNA. In turn, recombinational events during reverse transcription can result in the incorporation of cellular sequences into retroviral genomes. If the cellular sequences encode proteins involved in the control of cell growth, then the high or inappropriate expression of these sequences as part of the retroviral genome may cause the malignant transformation of the infected cell. Viruses of this type, that transduce cellular transforming genes, are known as acute transforming viruses. They can only arise in animals infected with replication-competent retroviruses, and in general cannot produce progeny viruses without replication-competent "helper" viruses. Since they are produced by a complex, multi-step pathway, acute transforming viruses are only generated at very low frequencies.
逆转录病毒通常以高保真度包装其基因组RNA。然而,这种保真度显然并不完美,因为一些细胞mRNA存在于标准逆转录病毒颗粒中。此外,源自整合前病毒5' LTR的转录本有时会延伸到前病毒的3' 端之外,导致产生包含病毒和细胞序列的嵌合RNA。这些RNA可以输出到细胞质中并包装到正在组装的病毒颗粒中。当这样的颗粒感染新的宿主细胞时,逆转录酶可能会将细胞序列以及病毒序列复制到DNA中。反过来,逆转录过程中的重组事件可能导致细胞序列整合到逆转录病毒基因组中。如果细胞序列编码参与细胞生长控制的蛋白质,那么作为逆转录病毒基因组一部分的这些序列的高表达或不适当表达可能会导致被感染细胞的恶性转化。这种转导细胞转化基因的病毒类型被称为急性转化病毒。它们只能在感染了具有复制能力的逆转录病毒的动物中产生,并且一般来说,没有具有复制能力的“辅助”病毒就不能产生子代病毒。由于它们是通过复杂的多步骤途径产生的,急性转化病毒仅以非常低的频率产生。