Kenyon Julia C, Ghazawi Akela, Cheung Winsome K S, Phillip Pretty S, Rizvi Tahir A, Lever Andrew M L
Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2QQ, United Kingdom.
RNA. 2008 Dec;14(12):2597-608. doi: 10.1261/rna.1284908. Epub 2008 Oct 30.
Feline immunodeficiency virus (FIV) is a lentivirus that infects cats and is related to human immunodeficiency virus (HIV). Although it is a common worldwide infection, and has potential uses as a human gene therapy vector and as a nonprimate model for HIV infection, little detail is known of the viral life cycle. Previous experiments have shown that its packaging signal includes two or more regions within the first 511 nucleotides of the genomic RNA. We have undertaken a secondary structural analysis of this RNA by minimal free-energy structural prediction, biochemical mapping, and phylogenetic analysis, and show that it contains five conserved stem-loops and a conserved long-range interaction between heptanucleotide sequences 5'-CCCUGUC-3' in R/U5 and 5'-GACAGGG-3' in gag. This long-range interaction is similar to that seen in primate lentiviruses where it is thought to be functionally important. Along with strains that infect domestic cats, this heptanucleotide interaction can also occur in species-specific FIV strains that infect pumas, lions, and Pallas' cats where the heptanucleotide sequences involved vary. We have analyzed spliced and genomic FIV RNAs and see little structural change or sequence conservation within single-stranded regions of the 5' UTR that are important for viral packaging, suggesting that FIV may employ a cotranslational packaging mechanism.
猫免疫缺陷病毒(FIV)是一种感染猫的慢病毒,与人类免疫缺陷病毒(HIV)相关。尽管它是一种全球范围内常见的感染病毒,并且具有作为人类基因治疗载体和HIV感染非灵长类动物模型的潜在用途,但对其病毒生命周期的了解却很少。先前的实验表明,其包装信号包括基因组RNA前511个核苷酸内的两个或更多区域。我们通过最小自由能结构预测、生化图谱分析和系统发育分析对该RNA进行了二级结构分析,结果表明它包含五个保守的茎环结构以及R/U5区域中七核苷酸序列5'-CCCUGUC-3'与gag区域中5'-GACAGGG-3'之间保守的长程相互作用。这种长程相互作用类似于灵长类慢病毒中观察到的相互作用,据认为在功能上很重要。除了感染家猫的毒株外,这种七核苷酸相互作用也可发生在感染美洲狮、狮子和兔狲的物种特异性FIV毒株中,只是所涉及的七核苷酸序列有所不同。我们分析了剪接后的FIV RNA和基因组FIV RNA,发现5'UTR单链区域内对于病毒包装很重要的区域几乎没有结构变化或序列保守性,这表明FIV可能采用共翻译包装机制。