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首页> 外文期刊>Journal of Molecular Biology >Optimal packaging of FIV genomic RNA depends upon a conserved long-range interaction and a palindromic sequence within gag.
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Optimal packaging of FIV genomic RNA depends upon a conserved long-range interaction and a palindromic sequence within gag.

机译：FIV基因组RNA的最佳包装取决于长距离相互作用和gag中的回文序列。

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The feline immunodeficiency virus (FIV) is a lentivirus that is related to human immunodeficiency virus (HIV), causing a similar pathology in cats. It is a potential small animal model for AIDS and the FIV-based vectors are also being pursued for human gene therapy. Previous studies have mapped the FIV packaging signal (psi) to two or more discontinuous regions within the 5' 511 nt of the genomic RNA and structural analyses have determined its secondary structure. The 5' and 3' sequences within psi region interact through extensive long-range interactions (LRIs), including a conserved heptanucleotide interaction between R/U5 and gag. Other secondary structural elements identified include a conserved 150 nt stem-loop (SL2) and a small palindromic stem-loop within gag open reading frame that might act as a viral dimerization initiation site. We have performed extensive mutational analysis of these sequences and structures and ascertained their importance in FIV packaging using a trans-complementation assay. Disrupting the conserved heptanucleotide LRI to prevent base pairing between R/U5 and gag reduced packaging by 2.8-5.5 fold. Restoration of pairing using an alternative, non-wild type (wt) LRI sequence restored RNA packaging and propagation to wt levels, suggesting that it is the structure of the LRI, rather than its sequence, that is important for FIV packaging. Disrupting the palindrome within gag reduced packaging by 1.5-3-fold, but substitution with a different palindromic sequence did not restore packaging completely, suggesting that the sequence of this region as well as its palindromic nature is important. Mutation of individual regions of SL2 did not have a pronounced effect on FIV packaging, suggesting that either it is the structure of SL2 as a whole that is necessary for optimal packaging, or that there is redundancy within this structure. The mutational analysis presented here has further validated the previously predicted RNA secondary structure of FIV psi.
机译：猫免疫缺陷病毒（FIV）是一种慢病毒，与人免疫缺陷病毒（HIV）有关，在猫中引起相似的病理。它是一种潜在的艾滋病小动物模型，基于FIV的载体也正在用于人类基因治疗。先前的研究已将FIV包装信号（psi）定位到基因组RNA 5'511 nt内的两个或多个不连续区域，并且结构分析确定了其二级结构。 psi区域内的5'和3'序列通过广泛的远程相互作用（LRI）进行相互作用，包括R / U5与gag之间的保守七核苷酸相互作用。确定的其他二级结构元件包括保守的150 nt茎环（SL2）和gag开放阅读框内的小回文茎环，可能起病毒二聚化起始位点的作用。我们已经对这些序列和结构进行了广泛的突变分析，并使用反式互补分析确定了它们在FIV包装中的重要性。破坏保守的七核苷酸LRI以防止R / U5和gag之间的碱基配对将包装减少了2.8-5.5倍。使用替代的非野生型（wt）LRI序列恢复配对可将RNA包装和繁殖恢复到wt水平，这表明LIV的结构而不是其序列对于FIV包装很重要。破坏gag内的回文使包装减少了1.5-3倍，但是用不同的回文序列取代并不能完全恢复包装，这表明该区域的序列及其回文性质很重要。 SL2单个区域的突变对FIV包装没有显着影响，表明要么是SL2的整体结构对于最佳包装是必需的，要么在此结构中存在冗余。本文介绍的突变分析进一步验证了先前预测的FIV psi RNA二级结构。

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