The intrinsic antiretroviral factor APOBEC3B contains two enzymatically active cytidine deaminase domains
The intrinsic antiretroviral factor APOBEC3B contains two enzymatically active cytidine deaminase domains
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DOI：
10.1016/j.virol.2007.03.019
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发表时间：
2007-08-01
期刊：
影响因子：
3.7
通讯作者：
Cullen, Bryan R.
中科院分区：
文献类型：
--
作者：
Bogerd, Hal P.;Wiegand, Heather L.;Cullen, Bryan R.
哺乳动物的APOBEC3蛋白是胞苷脱氨酶，可作为逆转录病毒复制和反转录转座子移动的抑制剂。一个一直存在争议的问题是，将脱氧胞苷残基编辑为脱氧尿苷对于这种抑制作用是否必要且充分，或者APOBEC3蛋白是否还发挥第二种独特的抑制机制。在此，我们对APOBEC3G和APOBEC3B的突变体抑制人类免疫缺陷病毒复制的能力进行了分析，这两种蛋白都包含两个共有胞苷脱氨酶活性位点。我们的数据证实APOBEC3G仅包含一个羧基末端活性位点，但令人惊讶的是，发现APOBEC3B中的两个胞苷脱氨酶共有序列都具有酶活性。发现无酶活性的APOBEC3G和APOBEC3B突变体形式分别保留了抑制在其存在下产生的HIV - 1病毒体感染性的能力，约为4倍和约8倍。虽然这种抑制作用明显低于野生型A3G或A3B所观察到的水平，但这些数据仍然表明APOBEC3蛋白对HIV - 1的抑制至少部分独立于DNA编辑。（c）2007年爱思唯尔公司。保留所有权利。
The mammalian APOBEC3 proteins are cytidine deaminases that function as inhibitors of retrovirus replication and retrotransposon mobility. An issue that has remained controversial is whether the editing of deoxycytidine residues to deoxyuridine is necessary and sufficient for this inhibition or whether APOBEC3 proteins also exert a second, distinct inhibitory mechanism. Here, we present an analysis of the ability of mutants of APOBEC3G and APOBEC3B, both of which contain two consensus cytidine deaminase active sites, to inhibit the replication of human immunodeficiency virus. Our data confirm that APOBEC3G only contains a single, carboxy-terminal active site but, surprisingly, reveal that both cytidine deaminase consensus sequences in APOBEC3B are enzymatically active. Enzymatically inactive mutant forms of APOBEC3G and APOBEC3B were found to retain the ability to inhibit the infectivity of HFV-1 virions produced in their presence by similar to 4-fold and similar to 8-fold, respectively. While this inhibition was significantly less than the level seen with wild-type forms of A3G or A3B, these data, nevertheless argue that the inhibition of HIV-1 by APOBEC3 proteins is at least partly independent of DNA editing. (c) 2007 Elsevier Inc. All rights reserved.