Vpr-mediated incorporation of UNG2 into HIV-1 particles is required to modulate the virus mutation rate and for replication in macrophages
Vpr-mediated incorporation of UNG2 into HIV-1 particles is required to modulate the virus mutation rate and for replication in macrophages
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DOI：
10.1074/jbc.m403875200
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发表时间：
2004-07-02
影响因子：
4.8
通讯作者：
Benichou, S
中科院分区：
文献类型：
--
作者：
Chen, RX;Le Rouzic, E;Benichou, S
人类免疫缺陷病毒1型能够感染非分裂细胞，如巨噬细胞，病毒Vpr蛋白已被证明参与这一过程。在这里，我们研究了招募到病毒颗粒的核形式的尿嘧啶DNA糖基化酶（UNG 2），细胞的DNA修复酶，对病毒突变率和复制在巨噬细胞的影响。我们证明，Vpr与UNG2的相互作用导致病毒粒子掺入催化活性酶，该酶直接参与Vpr调节病毒突变率。在原代单核细胞衍生的巨噬细胞中病毒复制期间病毒体中UNG的缺乏进一步加剧了病毒突变频率，与活跃分裂细胞中测量的4倍增加相比增加了18倍。由于UNG的存在对于巨噬细胞的有效感染也是至关重要的，这些观察结果将Vpr的作用扩展到病毒生命周期的另一个早期步骤，即。G.病毒DNA合成，对人类免疫缺陷病毒1型在非分裂细胞中的复制至关重要。
Human immunodeficiency virus type 1 is able to infect nondividing cells, such as macrophages, and the viral Vpr protein has been shown to participate in this process. Here, we investigated the impact of the recruitment into virus particles of the nuclear form of uracil DNA glycosylase (UNG2), a cellular DNA repair enzyme, on the virus mutation rate and on replication in macrophages. We demonstrate that the interaction of Vpr with UNG2 led to virion incorporation of a catalytically active enzyme that is directly involved with Vpr in modulating the virus mutation rate. The lack of UNG in virions during virus replication in primary monocyte-derived macrophages further exacerbated virus mutant frequencies to an 18-fold increase compared with the 4-fold increase measured in actively dividing cells. Because the presence of UNG is also critical for efficient infection of macrophages, these observations extend the role of Vpr to another early step of the virus life cycle, e. g. viral DNA synthesis, that is essential for replication of human immunodeficiency virus type 1 in nondividing cells.