Human immunodeficiency virus type 1 Vpr polymorphisms associated with progressor and nonprogressor individuals alter Vpr-associated functions.
Human immunodeficiency virus type 1 Vpr polymorphisms associated with progressor and nonprogressor individuals alter Vpr-associated functions.
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人类免疫缺陷病毒 1 型 Vpr 多态性与进展者和非进展者个体相关，会改变 Vpr 相关功能。
DOI：
10.1099/vir.0.059576-0
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Ayyavoo,Velpandi
中科院分区：
文献类型：
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作者：
Hadi,Kevin;Walker,LeahA;Guha,Debjani;Murali,Ramachandran;Watkins,SimonC;Tarwater,Patrick;Srinivasan,Alagarsamy;Ayyavoo,Velpandi
人类免疫缺陷病毒1（HIV-1）感染后，病毒复制和疾病进展发生显著变化。宿主和病毒因素都与观察到的疾病状态差异有关。在这里，我们专注于了解HIV-1病毒蛋白R（Vpr）的贡献，通过评估疾病相关的Vpr多态性及其生物学功能，从HIV-1阳性快速进展（RP）和长期非进展（LTNP）的主题。这里呈现的结果显示来自LTNP和RP受试者的Vpr等位基因的表型的不同变化。最值得注意的是，与RP相关的Vpr在R36 W和L 68 M处的多态性显示出更高水平的寡聚化和增加的病毒复制，而R77 Q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阻滞功能的相关性。总之，这些结果表明，Vpr的多态性部分可能有助于改变病毒复制动力学，导致LTNP和RP组中观察到的疾病进展差异。
Following infection withHuman 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.