Venkatachari Narasimhan J, Majumder Biswanath, Ayyavoo Velpandi
Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, 130 Desoto Street, Pittsburgh, PA 15261, USA.
Virology. 2007 Feb 20;358(2):347-56. doi: 10.1016/j.virol.2006.08.030. Epub 2006 Oct 4.
Human immunodeficiency virus type 1 (HIV-1) viral proteins disrupt the normal host cellular immune pathways thus exploiting the cellular machinery for replication, survival and to escape host immune attack. Here we evaluated the direct effects of HIV-1 Vpr-mediated immune modulation of infected T cells. Vpr specifically downregulated the expression of CD28 and increased the expression of CTLA-4, whereas no significant difference in the expression of CD25 and HLA-DR was observed. Interferon gamma (IFN-gamma) production in T cells was evaluated as a measure of the downstream effector functions. Results indicate that Vpr significantly inhibited IFN-gamma production and this may, in part, due to Vpr's ability to inhibit the nuclear translocation of NF-kappaB, and its transcriptional regulation. Together these results support that HIV-1 Vpr selectively dysregulates the immune functions at multiple levels and exerts its inhibitory effects in the presence of other viral proteins.
1型人类免疫缺陷病毒（HIV-1）的病毒蛋白会破坏正常的宿主细胞免疫途径，从而利用细胞机制进行复制、存活并逃避宿主的免疫攻击。在此，我们评估了HIV-1 Vpr介导的对受感染T细胞免疫调节的直接作用。Vpr特异性地下调了CD28的表达并增加了CTLA-4的表达，而CD25和HLA-DR的表达未观察到显著差异。T细胞中γ干扰素（IFN-γ）的产生被评估为下游效应功能的一个指标。结果表明，Vpr显著抑制了IFN-γ的产生，这可能部分归因于Vpr抑制核因子κB核转位及其转录调控的能力。这些结果共同支持，HIV-1 Vpr在多个水平上选择性地失调免疫功能，并在存在其他病毒蛋白的情况下发挥其抑制作用。
