VPR IS REQUIRED FOR EFFICIENT REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN MONONUCLEAR PHAGOCYTES
VPR IS REQUIRED FOR EFFICIENT REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN MONONUCLEAR PHAGOCYTES
复制标题
DOI：
10.1006/viro.1995.1016
复制
发表时间：
1995-02-01
期刊：
影响因子：
3.7
通讯作者：
LANDAU, NR
中科院分区：
文献类型：
--
作者：
CONNOR, RI;CHEN, BK;LANDAU, NR
HIV-1 vpr编码一个96个氨基酸的核蛋白，其功能尚不清楚。与其他慢病毒调节蛋白不同，Vpr以相对高的拷贝数存在于病毒体中。在细胞中，Vpr定位于细胞核。与这些发现一致的vpr可能的功能包括整合前复合物的核输入，细胞基因的反式激活或细胞分化的诱导。我们在这里显示，使用复制能力，嗜巨噬细胞病毒和敏感的，单循环荧光素酶HIV-1报告载体，Vpr是重要的有效的病毒复制在初级单核细胞/巨噬细胞，但似乎没有发挥作用，在活化或静息T细胞感染。通过PCR分析新合成的病毒DNA和荧光素酶报告载体，将单核细胞中的感染阻断定位于病毒生命周期中进入和逆转录后的阶段，但在前病毒转录之前或之时。此外，已加载Vpr分子的生产细胞通过反式互补的病毒粒子的单核吞噬细胞的感染仍然表现出Vpr表型。这些数据表明vpr分子在新感染细胞中产生的作用，除了它在病毒体中的假定功能。(C)出版社：Academic Press
HIV-1 vpr encodes a 96-amino acid, nuclear protein whose function is not well understood. Unlike the other lentivirus regulatory proteins, Vpr is present in Virions at relatively high copy number. In cells, Vpr is localized to the nucleus. Possible functions for vpr consistent with these findings include the nuclear import of preintegration complexes, transactivation of cellular genes, or induction of cellular differentiation. We show here, using both replication competent, macrophage-tropic virus and a sensitive, single-cycle luciferase HIV-1 reporter vector, that vpr is important for efficient viral replication in primary monocyte/macrophages, but appears to play no role in activated or resting T cell infection. The block to infection in monocytes was localized by PCR analysis of newly synthesized viral DNA and with the luciferase reporter vector to a stage in the viral life cycle after entry and reverse transcription, yet prior to, or at the time of, proviral transcription. In addition, infection of mononuclear phagocytes with virions that had been loaded with Vpr molecules in the producer cells by trans-complementation still showed a vpr-phenotype. These data suggest a role for vpr molecules produced in newly infected cells, in addition to its presumed function in the virion. (C) 1995 Academic Press, Inc.