Department of Microbiology & Immunology, Faculty of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates.
Virus Res. 2011 Jan;155(1):352-7. doi: 10.1016/j.virusres.2010.09.018. Epub 2010 Sep 25.
Retroviral RNA packaging signal (ψ) allows the preferential packaging of genomic RNA into virus particles through its interaction with the nucleocapsid protein. The specificity of this interaction came into question when it was shown that primate retroviruses, such as HIV-1, could cross-package RNA from its simian cousin, SIV, and vice versa and that feline retrovirus, FIV could cross-package RNA from a distantly related primate retrovirus, MPMV. To study the generality of this phenomenon further, we determined whether there is a greater packaging restriction between the lentiviral class of retroviruses (HIV-1 and SIV) and a non-lentivirus, MPMV. Our results revealed that primate lentiviral RNAs can be cross-packaged by primate non-lentiviral particles reciprocally, but the cross-packaged RNAs could not be propagated by the heterologous particles. Packaging of RNA in the context of both retroviral vectors as well as non-retroviral RNA containing SIV, HIV, and MPMV packaging determinants by each others proteins further confirmed the specificity of cross-packaging conferred by the packaging sequences. These results reveal the promiscuous nature of retroviral packaging determinants and raise caution against their wide spread presence on retroviral vectors to be used for human gene therapy.
逆转录病毒 RNA 包装信号（ψ）允许通过其与核衣壳蛋白的相互作用，优先将基因组 RNA 包装到病毒颗粒中。当表明灵长类逆转录病毒，如 HIV-1，可以交叉包装来自其灵长类表亲 SIV 的 RNA，反之亦然，并且猫科逆转录病毒 FIV 可以交叉包装来自远亲灵长类逆转录病毒 MPMV 的 RNA 时，这种相互作用的特异性就受到了质疑。为了进一步研究这种现象的普遍性，我们确定了在慢病毒类逆转录病毒（HIV-1 和 SIV）和非慢病毒之间是否存在更大的包装限制，MPMV。我们的结果表明，灵长类慢病毒 RNA 可以被灵长类非慢病毒颗粒交叉包装，但异源颗粒不能复制交叉包装的 RNA。在逆转录病毒载体的背景下以及包含 SIV、HIV 和 MPMV 包装决定因素的非逆转录病毒 RNA 中包装 RNA，进一步证实了包装序列赋予的交叉包装的特异性。这些结果揭示了逆转录病毒包装决定因素的混杂性质，并提醒人们注意它们在用于人类基因治疗的逆转录病毒载体中的广泛存在。
