CBFβ对HIV-1 Vif蛋白功能及结构影响的机制研究

发布时间：2018-05-30 06:55

本文选题：HIV-1 + vif　；参考：《吉林大学》2012年博士论文

【摘要】：人类的APOBEC3胞嘧啶脱氨酶是多种逆转录病毒(包括HIV1)的抑制因子。而HIV1Vif（viral infectivity factor）通过与宿主细胞的Cullin5（Cul5）,Elongin B和Elongin C形成E3泛素连接酶复合体，使APOBEC3底物蛋白泛素化及蛋白酶降解途径降解，从而对抗其抗病毒活性。最近，CBFβ（core binding factor β）被证实在HIV1对抗宿主APOBEC3蛋白的过程中起重要的调节作用。本论文在此研究的基础上，进一步证明除了HIV1Vif，CBFβ对SIV（simian immunodeficiency virus） vif的功能也有重要的调节作用。但是CBFβ对BIV（bovine immunodeficiency virus）和FIV（feline immunodeficiency virus）却没有这种调节作用，说明慢病毒的Vif蛋白在其抑制相应种属的APOBEC3蛋白时存在进化保守性。本论文还证明了CBFβ主要通过调节Vif与Cul5之间的相互作用来调节vif的功能，而并非通过调节vif的稳定性。另外，本论文还对vif蛋白的表达和纯化做了进一步研究。通过联合表达HIV1vif和CBF β，显著增加了vif蛋白的可溶性，这对vif蛋白的结构学研究有重要意义。
[Abstract]:Human APOBEC3 cytosine deaminase is an inhibitor of multiple retroviruses, including HIV 1. HIV1Vif(viral infectivity factor forms an E3 ubiquitin ligase complex with the host cell cullin5, Cullongin B and Elongin C, which degrades the APOBEC3 substrate protein ubiquification and protease degradation pathway, thus antagonizing its antiviral activity. Recently, CBF 尾 core binding factor 尾 has been demonstrated to play an important regulatory role in the process of HIV1 against host APOBEC3 protein. On the basis of this study, it is further proved that CBF- 尾 plays an important role in regulating the function of SIV(simian immunodeficiency virus) vif in addition to HIV-1. However, CBF 尾 had no such regulation on BIV(bovine immunodeficiency virusand FIV(feline immunodeficiency virus. suggesting that lentivirus Vif protein is evolutionarily conserved when it inhibits the APOBEC3 protein of the corresponding species. This paper also proves that CBF 尾 regulates the function of vif mainly by regulating the interaction between Vif and Cul5, but not by regulating the stability of vif. In addition, the expression and purification of vif protein were further studied. By co-expression of HIV1vif and CBF 尾, the solubility of vif protein was significantly increased, which is of great significance for the structural study of vif protein.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R512.91;R373

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