Role of matrix in an early postentry step in the human immunodeficiency virus type 1 life cycle
Role of matrix in an early postentry step in the human immunodeficiency virus type 1 life cycle
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DOI：
10.1128/jvi.72.5.4116-4126.1998
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发表时间：
1998-05-01
影响因子：
5.4
通讯作者：
Freed, EO
中科院分区：
文献类型：
--
作者：
Kiernan, RE;Ono, A;Freed, EO
据报道，人类免疫缺陷病毒1型（HIV-1）的基质蛋白在Gag多聚蛋白前体靶向质膜和将病毒包膜糖蛋白掺入出芽病毒体中中起关键作用。在这份报告中，我们提出的证据表明，在基质氨基酸20块高度保守的亮氨酸突变或显着延迟病毒复制在一系列的细胞类型，包括T细胞系，原代人外周血单核细胞，单核细胞衍生的巨噬细胞。这些突变不损害病毒装配和释放，RNA的结合，或包膜糖蛋白掺入病毒粒子，而是在病毒生命周期的早期步骤中引起显着的缺陷，如通过单周期感染性测定和分析病毒DNA合成感染后早期。这种感染性缺陷不依赖于突变病毒粒子上携带的包膜糖蛋白的类型;在使用野生型或截短的HIV-1包膜糖蛋白、嗜酸性鼠白血病病毒包膜或水泡性口炎G蛋白的假型实验中获得了类似的结果。有趣的是，基质残基20突变也增加了Gag与膜的表观结合，加速了Gag加工的动力学，这些结果有助于阐明基质在HIV-1复制中的作用。
The matrix protein of human immunodeficiency virus type 1 (HIV-1) has been reported to play a crucial role in the targeting of the Gag polyprotein precursor to the plasma membrane and in the incorporation of viral envelope glycoproteins into budding virions. In this report, we present evidence that mutation of a highly conserved Leu at matrix amino acid 20 blocks or markedly delays virus replication in a range of cell types, including T-cell lines, primary human peripheral blood mononuclear cells, and monocyte-derived macrophages. These mutations do not impair virus assembly and release, RNA encapsidation, or envelope glycoprotein incorporation into virions but rather cause significant defects in an early step in the virus life cycle, as measured by single-cycle infectivity assays and the analysis of viral DNA synthesis early postinfection. This infectivity defect is independent of the type of envelope glycoprotein carried on mutant virions; similar results are obtained in pseudotyping experiments using wild-type or truncated HIV-1 envelope glycoproteins, the amphotropic murine leukemia virus envelope, or the vesicular stomatitis G protein, Intriguingly, matrix residue 20 mutations also increase the apparent binding of Gag to membrane, accelerate the kinetics of Gag processing, and induce defects in endogenous reverse transcriptase activity without affecting virion density or morphology, These results help elucidate the function of matrix in HIV-1 replication.