Hultquist Judd F, Harris Reuben S
Department of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, MN 55455, USA Tel.: +1 414 702 7232,
Future Virol. 2009 Nov 1;4(6):605. doi: 10.2217/fvl.09.59.
At least two human APOBEC3 proteins - APOBEC3F and APOBEC3G - are capable of inhibiting HIV-1 replication by mutation of the viral cDNA. HIV-1 averts lethal restriction through its accessory protein Vif, which targets these APOBEC3 proteins for proteasomal degradation. The life-or-death interaction between human APOBEC3 proteins and HIV-1 Vif has stimulated much interest in developing novel therapeutics aimed at altering the deaminase activity of the APOBEC3s, thus changing the virus' mutation rate to either lethal or suboptimal levels. The current state of mechanistic information is reviewed and the possible risks and benefits of increasing (via hypermutation) or decreasing (via hypomutation) the HIV-1 mutation rate through APOBEC3 proteins are discussed.
至少两种人类载脂蛋白B mRNA编辑酶催化多肽样蛋白3(APOBEC3)——APOBEC3F和APOBEC3G——能够通过病毒cDNA的突变来抑制HIV-1复制。HIV-1通过其辅助蛋白Vif避免致命的限制,Vif将这些APOBEC3蛋白靶向蛋白酶体降解。人类APOBEC3蛋白与HIV-1 Vif之间的生死相互作用激发了人们对开发新型疗法的浓厚兴趣,这些疗法旨在改变APOBEC3的脱氨酶活性,从而将病毒的突变率改变到致死或次优水平。本文综述了机制信息的现状,并讨论了通过APOBEC3蛋白增加(通过超突变)或降低(通过低突变)HIV-1突变率可能带来的风险和益处。