Cellular HIV-1 inhibition by truncated old world primate APOBEC3A proteins lacking a complete deaminase domain.
Cellular HIV-1 inhibition by truncated old world primate APOBEC3A proteins lacking a complete deaminase domain.
复制标题
缺乏完整脱氨酶结构域的截短旧世界灵长类动物 APOBEC3A 蛋白对细胞 HIV-1 的抑制作用。
DOI：
10.1016/j.virol.2014.09.001
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Stephens,EdwardB
中科院分区：
文献类型：
--
作者：
Katuwal,Miki;Wang,Yaqiong;Schmitt,Kimberly;Guo,Kejun;Halemano,Kalani;Santiago,MarioL;Stephens,EdwardB
APOBEC 3（A3）脱氨酶是逆转录病毒限制性因子，被提议作为HIV-1基因治疗载体的抑制组分。然而，A3突变活性可能会诱导不希望的基因组损伤，并使HIV-1能够逃避药物和免疫反应。在这里，我们表明，A3 A蛋白从colA 3A（colA 3A）可以限制HIV-1复制生产细胞中的脱氨酶不依赖的方式，而不诱导DNA损伤。ColA 3A对HIV-1的逆转录和整合均无显著影响，但对衣壳蛋白的合成有抑制作用。colA 3A限制性酶的决定簇定位于N-末端区域。这些性质延伸到A3 A从山鸡和德布拉扎的猴子。令人惊讶的是，截短的colA 3A蛋白只表达N-末端100个氨基酸有效地排除关键的催化区域，但保留了有效的细胞限制活性。这些突出了几种旧大陆猴A3 A蛋白的细胞HIV-1限制的独特机制，可用于功能性HIV-1治疗策略。
The APOBEC3 (A3) deaminases are retrovirus restriction factors that were proposed as inhibitory components of HIV-1 gene therapy vectors. However, A3 mutational activity may induce undesired genomic damage and enable HIV-1 to evade drugs and immune responses. Here, we show that A3A protein fromColobus guereza(colA3A) can restrict HIV-1 replication in producer cells in a deaminase-independent manner without inducing DNA damage. Neither HIV-1 reverse transcription nor integration were significantly affected by colA3A, but capsid protein synthesis was inhibited. The determinants for colA3A restriction mapped to the N-terminal region. These properties extend to A3A from mandrills and De Brazza׳s monkeys. Surprisingly, truncated colA3A proteins expressing only the N-terminal 100 amino acids effectively exclude critical catalytic regions but retained potent cellular restriction activity. These highlight a unique mechanism of cellular HIV-1 restriction by several Old World monkey A3A proteins that may be exploited for functional HIV-1 cure strategies.