Cadima-Couto Iris, Goncalves Joao
URIA-Centro Patogénese Molecular and Instituto de Medicina Molecular, Faculdade de Farmácia da Universidade Lisboa, Avenue Das Forcas Armadas, 1649-019 Lisboa, Portugal.
Adv Virol. 2010;2010:649315. doi: 10.1155/2010/649315. Epub 2010 Sep 21.
APOBEC proteins appeared in the cellular battle against HIV-1 as part of intrinsic cellular immunity. The antiretroviral activity of some of these proteins is overtaken by the action of HIV-1 Viral Infectivity Factor (Vif) protein. Since the discovery of APOBEC3G (A3G) as an antiviral factor, many advances have been made to understand its mechanism of action in the cell and how Vif acts in order to counteract its activity. The mainstream concept is that Vif overcomes the innate antiviral activity of A3G by direct protein binding and promoting its degradation via the cellular ubiquitin/proteasomal pathway. Vif may also inhibit A3G through mechanisms independent of proteasomal degradation. Binding of Vif to A3G is essential for its degradation since disruption of this interaction is predicted to stimulate intracellular antiviral immunity. In this paper we will discuss the different binding partners between both proteins as one of the major challenges for the development of new antiviral drugs.
载脂蛋白B mRNA编辑酶催化多肽样蛋白（APOBEC）作为固有细胞免疫的一部分，出现在细胞对抗HIV-1的战斗中。其中一些蛋白质的抗逆转录病毒活性被HIV-1病毒感染因子（Vif）蛋白的作用所抵消。自从发现载脂蛋白B mRNA编辑酶催化多肽样蛋白3G（A3G）作为一种抗病毒因子以来，在理解其在细胞中的作用机制以及Vif如何发挥作用以抵消其活性方面已经取得了许多进展。主流观点是，Vif通过直接蛋白质结合并促进其通过细胞泛素/蛋白酶体途径降解，来克服A3G的固有抗病毒活性。Vif也可能通过独立于蛋白酶体降解的机制抑制A3G。Vif与A3G的结合对其降解至关重要，因为这种相互作用的破坏预计会刺激细胞内抗病毒免疫。在本文中，我们将讨论这两种蛋白质之间不同的结合伙伴，这是开发新型抗病毒药物的主要挑战之一。
