Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA.
Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, USA.
J Gen Virol. 2014 Mar;95(Pt 3):700-711. doi: 10.1099/vir.0.059576-0. Epub 2013 Dec 3.
Following infection with Human immunodeficiency virus 1 (HIV-1) there is a remarkable variation in virus replication and disease progression. Both host and viral factors have been implicated in the observed differences in disease status. Here, we focus on understanding the contribution of HIV-1 viral protein R (Vpr) by evaluating the disease-associated Vpr polymorphism and its biological functions from HIV-1 positive rapid progressor (RP) and long-term nonprogressor (LTNP) subjects. Results presented here show distinct variation in phenotypes of Vpr alleles from LTNP and RP subjects. Most notably, the polymorphism of Vpr at R36W and L68M associated with RP shows higher levels of oligomerization, and increased virus replication, whereas R77Q exhibits poor replication kinetics. Interestingly, we did not observe correlation with cell cycle arrest function. Together these results indicate that polymorphisms in Vpr in part may contribute to altered virus replication kinetics leading to the observed differences in disease progression in LTNP and RP groups.
感染人类免疫缺陷病毒 1 型（HIV-1）后，病毒复制和疾病进展存在显著差异。宿主和病毒因素都与观察到的疾病状态差异有关。在这里，我们通过评估 HIV-1 阳性快速进展者（RP）和长期非进展者（LTNP）个体中与疾病相关的 Vpr 多态性及其生物学功能，重点研究 HIV-1 病毒蛋白 R（Vpr）的作用。本文结果显示，来自 LTNP 和 RP 个体的 Vpr 等位基因表型存在明显差异。值得注意的是，与 RP 相关的 Vpr 第 36 位精氨酸（R）到色氨酸（W）和第 68 位亮氨酸（L）到蛋氨酸（M）的多态性显示出更高的寡聚化水平和增强的病毒复制能力，而第 77 位精氨酸（R）到谷氨酰胺（Q）则表现出较差的复制动力学。有趣的是，我们没有观察到与细胞周期停滞功能的相关性。综上所述，这些结果表明，Vpr 中的多态性可能在一定程度上导致病毒复制动力学的改变，从而导致 LTNP 和 RP 组疾病进展的差异。
