Poon Betty, Chang Michael A, Chen Irvin S Y
Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, UCLA AIDS Institute and Jonsson Comprehensive CAncer Center, 11-934 Factor Building, 10833 Le Conte Avenue, Los Angeles, CA 90095-1678, USA.
J Virol. 2007 Oct;81(19):10515-23. doi: 10.1128/JVI.00947-07. Epub 2007 Jul 25.
Unintegrated human immunodeficiency virus (HIV) DNA are viral DNA products formed naturally during HIV replication. While the integrated proviral DNA form is transcriptionally active and results in productive infection, unintegrated DNA is also capable of expression of viral RNA and proteins. Previously, we showed that HIV Vpr enhances expression from integrase-defective HIV. Here we show that Vpr activation of expression is partially dependent upon the presence of a transcriptionally active HIV promoter and results in increased transcription of unspliced gag and spliced nef viral RNA. While Tat is detectable during infection with integrase-defective HIV, Tat levels are not affected by the presence of Vpr. Mutation studies reveal that Tat is dispensable for the Vpr-mediated enhancement of expression from unintegrated DNA. We find that virion-associated Vpr is sufficient for Nef expression from unintegrated viral DNA, resulting in the efficient downregulation of CD4 from the surface of infected cells. These results provide a mechanism by which Nef expression from unintegrated HIV type 1 DNA expression occurs.
未整合的人类免疫缺陷病毒（HIV）DNA是HIV复制过程中自然形成的病毒DNA产物。虽然整合的前病毒DNA形式具有转录活性并导致 productive 感染，但未整合的DNA也能够表达病毒RNA和蛋白质。此前，我们发现HIV Vpr可增强整合酶缺陷型HIV的表达。在此我们表明，Vpr对表达的激活部分依赖于转录活性HIV启动子的存在，并导致未剪接的gag和剪接的nef病毒RNA转录增加。虽然在整合酶缺陷型HIV感染期间可检测到Tat，但Tat水平不受Vpr存在的影响。突变研究表明，Tat对于Vpr介导的未整合DNA表达增强是可有可无的。我们发现病毒体相关的Vpr足以从未整合的病毒DNA表达Nef，从而有效地从感染细胞表面下调CD4。这些结果提供了一种机制，通过该机制可从未整合的1型HIV DNA表达Nef。
