Phosphorylation of Vpr regulates HIV type 1 nuclear import and macrophage infection
Phosphorylation of Vpr regulates HIV type 1 nuclear import and macrophage infection
复制标题
DOI：
10.1089/088922202753472856
复制
发表时间：
2002-03-01
影响因子：
1.5
通讯作者：
Bukrinsky, M
中科院分区：
文献类型：
--
作者：
Agostini, I;Popov, S;Bukrinsky, M
人类免疫缺陷病毒1型（HIV-1）的病毒蛋白R （Vpr）是一种小的辅助蛋白，它调节病毒前整合复合体的核输入，促进非分裂细胞（如巨噬细胞）的感染。研究表明，部分Vpr分子在病毒粒子和hiv -1感染细胞中被磷酸化，但磷酸化在Vpr核输入活性中的作用尚未确定。我们发现Vpr主要在79位丝氨酸残基上磷酸化，影响Vpr磷酸化的突变显著减弱了巨噬细胞中的病毒复制，但在活化的T淋巴细胞或细胞系中没有。通过聚合酶链反应分析，将复制缺陷定位到核输入环节。这些结果表明，Vpr的磷酸化调节了其在HIV-1预整合复合体核输入中的活性。
Viral protein R (Vpr) of human immunodeficiency virus type 1 (HIV-1) is a small accessory protein that regulates nuclear import of the viral preintegration complex and facilitates infection of nondividing cells, such as macrophages. Studies demonstrated that a fraction of Vpr molecules is phosphorylated in the virions and in HIV-1-infected cells, but the role of phosphorylation in nuclear import activity of Vpr has not been established. We found that Vpr is phosphorylated predominantly on the serine residue in position 79, and mutations affecting Vpr phosphorylation significantly attenuated viral replication in macrophages, but not in activated T lymphocytes or cell lines. The replication defect was mapped by polymerase chain reaction analysis to the step of nuclear import. These results suggest that phosphorylation of Vpr regulates its activity in the nuclear import of the HIV-1 preintegration complex.