OyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USA.
OyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USA.
Trends Mol Med. 2018 May;24(5):507-520. doi: 10.1016/j.molmed.2018.03.004. Epub 2018 Mar 30.
The infectivity of HIV depends on overcoming APOBEC3 (A3) innate immunity, predominantly through the expression of the viral protein Vif, which induces A3 degradation in the proteasome. Disruption of the functional interactions of Vif enables A3 mutagenesis of the HIV genome during viral replication, which can result in a broadly neutralizing antiviral effect. Vif function requires self-association along with interactions with A3 proteins, protein chaperones, and factors of the ubiquitination machinery and these are described here as a potential platform for novel antiviral drug discovery. This Review will examine the current state of development of Vif inhibitors that we believe to have therapeutic and functional cure potential.
HIV 的感染力取决于克服 APOBEC3(A3)先天免疫,主要通过表达病毒蛋白 Vif 来实现,Vif 诱导 A3 在蛋白酶体中降解。破坏 Vif 的功能相互作用可使 A3 在病毒复制过程中对 HIV 基因组进行突变,从而产生广泛中和的抗病毒作用。Vif 的功能需要自身缔合以及与 A3 蛋白、蛋白伴侣和泛素化机制的因子相互作用,这些作用在这里被描述为一个有潜力的新型抗病毒药物发现平台。本综述将考察我们认为具有治疗和功能性治愈潜力的 Vif 抑制剂的开发现状。