Kaddis Maldonado Rebecca J, Parent Leslie J
Division of Infectious Diseases and Epidemiology, Department of Medicine, Penn State College of Medicine, 500 University Drive, Hershey PA 17033, USA.
Department of Microbiology and Immunology, Penn State College of Medicine, 500 University Drive, Hershey PA 17033, USA.
Viruses. 2016 Sep 20;8(9):257. doi: 10.3390/v8090257.
Infectious retrovirus particles contain two copies of unspliced viral RNA that serve as the viral genome. Unspliced retroviral RNA is transcribed in the nucleus by the host RNA polymerase II and has three potential fates: (1) it can be spliced into subgenomic messenger RNAs (mRNAs) for the translation of viral proteins; or it can remain unspliced to serve as either (2) the mRNA for the translation of Gag and Gag-Pol; or (3) the genomic RNA (gRNA) that is packaged into virions. The Gag structural protein recognizes and binds the unspliced viral RNA to select it as a genome, which is selected in preference to spliced viral RNAs and cellular RNAs. In this review, we summarize the current state of understanding about how retroviral packaging is orchestrated within the cell and explore potential new mechanisms based on recent discoveries in the field. We discuss the -acting elements in the unspliced viral RNA and the properties of the Gag protein that are required for their interaction. In addition, we discuss the role of host factors in influencing the fate of the newly transcribed viral RNA, current models for how retroviruses distinguish unspliced viral mRNA from viral genomic RNA, and the possible subcellular sites of genomic RNA dimerization and selection by Gag. Although this review centers primarily on the wealth of data available for the alpharetrovirus Rous sarcoma virus, in which a discrete RNA packaging sequence has been identified, we have also summarized the - and -acting factors as well as the mechanisms governing gRNA packaging of other retroviruses for comparison.
传染性逆转录病毒颗粒包含两份未剪接的病毒RNA,它们作为病毒基因组。未剪接的逆转录病毒RNA在细胞核中由宿主RNA聚合酶II转录,有三种潜在命运:(1)它可以被剪接成亚基因组信使RNA(mRNA)用于病毒蛋白的翻译;或者它可以保持未剪接状态,用作(2)用于翻译Gag和Gag-Pol的mRNA;或者(3)被包装到病毒粒子中的基因组RNA(gRNA)。Gag结构蛋白识别并结合未剪接的病毒RNA以将其选为基因组,相对于剪接的病毒RNA和细胞RNA,它优先被选中。在本综述中,我们总结了目前对逆转录病毒在细胞内如何进行包装的理解现状,并基于该领域的最新发现探索潜在的新机制。我们讨论了未剪接病毒RNA中的顺式作用元件以及它们相互作用所需的Gag蛋白的特性。此外,我们讨论了宿主因子在影响新转录的病毒RNA命运方面的作用、逆转录病毒如何区分未剪接的病毒mRNA和病毒基因组RNA的当前模型,以及基因组RNA二聚化和被Gag选择的可能亚细胞位点。尽管本综述主要集中在可获得大量数据的α逆转录病毒劳斯肉瘤病毒上,其中已鉴定出一个离散的RNA包装序列,但我们也总结了其他逆转录病毒的顺式和反式作用因子以及控制gRNA包装的机制以作比较。