Kondo E, Göttlinger H G
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
J Virol. 1996 Jan;70(1):159-64. doi: 10.1128/JVI.70.1.159-164.1996.
The vpr gene product of human immunodeficiency virus type (HIV-1) is a virion-associated regulatory protein. A transferable virion association motif for Vpr is located in the p6 domain of the HIV-1 Gag polyprotein. To map the sequences in p6 that are involved in Vpr incorporation, we analyzed the ability of mutant forms of p6 to direct the incorporation of Vpr into chimeric viral particles. Our results show that the determinants which govern Vpr incorporation are largely confined to a C-terminal region of the p6 domain. Within this region, three hydrophobic residues in a highly conserved sequence motif (L-X-S-L-F-G) are absolutely required. Remarkably, the transfer of the conserved motif and of a single flanking residue to a heterologous Gag polyprotein was sufficient to transfer the ability to incorporate Vpr at moderate levels. The transfer of residues 32 to 46 of p6 led to Vpr incorporation levels that were comparable to those obtained with full-length HIV-1 Gag protein, indicating that this region contains essentially all the information required for efficient Vpr incorporation.
人类免疫缺陷病毒1型(HIV-1)的vpr基因产物是一种与病毒体相关的调节蛋白。Vpr的一个可转移的病毒体关联基序位于HIV-1 Gag多聚蛋白的p6结构域中。为了定位p6中参与Vpr整合的序列,我们分析了p6突变形式引导Vpr整合到嵌合病毒颗粒中的能力。我们的结果表明,控制Vpr整合的决定因素主要局限于p6结构域的C末端区域。在该区域内,一个高度保守的序列基序(L-X-S-L-F-G)中的三个疏水残基是绝对必需的。值得注意的是,将保守基序和单个侧翼残基转移到异源Gag多聚蛋白上足以转移以中等水平整合Vpr的能力。p6的32至46位残基的转移导致Vpr整合水平与全长HIV-1 Gag蛋白获得的水平相当,表明该区域基本上包含有效整合Vpr所需的所有信息。