A chimeric human APOBEC3A protein with a three amino acid insertion confers differential HIV-1 and adeno-associated virus restriction.
A chimeric human APOBEC3A protein with a three amino acid insertion confers differential HIV-1 and adeno-associated virus restriction.
复制标题
DOI：
10.1016/j.virol.2016.08.001
复制
发表时间：
2016-11
期刊：
影响因子：
3.7
通讯作者：
Yaqiong Wang;Zekun Wang;A. Pramanik;M. Santiago;J. Qiu;E. Stephens
中科院分区：
文献类型：
--
作者：
Yaqiong Wang;Zekun Wang;A. Pramanik;M. Santiago;J. Qiu;E. Stephens
旧大陆猴（OWM）和人类apobec3a蛋白对慢病毒和DNA病毒表现出不同的限制性活性。人类APOBEC3A（hA3A）对HIV-1Δvifbut的限制性活性较弱，被人工合成的山魈嵌合物（mndA3A/G）有效限制。我们发现含有“WVS”插入的嵌合ha3 （hA3A[27WVS29]）具有有效的hiv -1限制性活性。对“WVS”基序的每个氨基酸的分析表明，限制活性与氨基酸的长度有关，而不一定是氨基酸的荷电性或疏水性。我们的研究结果表明，hA3A[27WVS29]在靶细胞的逆转录水平上限制hiv -1。最后，我们的研究结果表明，在ha3中插入“WVS”可以适度减少对腺相关病毒2（AAV-2）的限制，而将mndA3A/G的AC loop1区域插入hA3A则可以消除对AAV-2的限制，从而加强了该分子界面在灵长类动物A3A功能进化中的作用。
Old World monkey (OWM) and hominid APOBEC3Aproteins exhibit differential restriction activities against lentiviruses and DNA viruses. Human APOBEC3A(hA3A)has weak restriction activity against HIV-1Δvifbut is efficiently restricted by an artificially generated chimeric from mandrills (mndA3A/G). We show that a chimeric hA3Acontaining the “WVS” insertion (hA3A[27WVS29]) conferred potent HIV-1restriction activity. Analysis of each amino acid of the “WVS” motif show that the length and not necessarily the charge or hydrophobicity of the amino acids accounted for restriction activity. Our results suggest that hA3A[27WVS29]restricts HIV-1at the level of reverse transcription in target cells. Finally, our results suggest that insertion of “WVS” into hA3Amodestly reduces restriction of adeno-associated virus 2(AAV-2)while insertion of the AC Loop1region of the mndA3A/G into hA3A abolished AAV-2 restriction, strengthening the role of this molecular interface in the functional evolution of primate A3A.