Mechanism of resistance to and regulation of APOBEC3 antiviral activity

在病毒-宿主相互作用领域，抗病毒胞苷脱氨酶APOBEC 3和逆转录病毒的相互作用是一个相当新的研究领域。人免疫缺陷病毒（HIV）是一种慢病毒，通过其蛋白Vif抵消APOBEC-3F/-3G的抗病毒活性。Vif诱导APOBEC 3的蛋白酶体降解。最近，我们发现属于另一个逆转录病毒亚科的泡沫病毒也通过一种称为Bet的辅助蛋白来中和APOBEC 3蛋白。初步数据表明，Bet对APOBEC 3的抑制不涉及蛋白质降解。第一个目的是分析Bet如何保护逆转录病毒对抗APOBEC 3的机制。APOBEC 3G活性的翻译后调节也是未知的。在第二个项目中，我们将研究Vif，Bet和APOBEC 3的宿主细胞调节磷酸化对其功能的作用。更好地了解Vif-APOBEC 3和Bet-APOBEC 3的相互作用可能为未来抗HIV-1药物的发现和开发提供途径。

In the field of viral-host interactions, the interplay of the antiviral cytidine-deaminating enzyme APOBEC3 and retroviruses is a rather new area of research. The human immunodeficiency virus (HIV), a lentivirus, counteracts the anti-viral activity of APOBEC-3F/-3G by its protein Vif. Vif induces a proteasomal degradation of APOBEC3. Recently we discovered that foamy viruses, which belong to another retrovirus subfamily, also neutralize APOBEC3 proteins by an accessory protein, called Bet. Preliminary data indicate that APOBEC3 suppression by Bet does not involve protein degradation. The first aim is to analyse the mechanism of how Bet protects retroviruses against APOBEC3. Unknown as well is the post-translational regulation of APOBEC3G activity. In the second project we will investigate the role of host-cell regulated phosphorylation of Vif, Bet and APOBEC3 for its functions. A better understanding of the interactions of Vif-APOBEC3 and Bet-APOBEC3 may pose an avenue for future anti HIV-1 drug discovery and development.