Interactions between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly
Interactions between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly
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DOI：
10.1128/jvi.02319-16
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发表时间：
2017-08-01
影响因子：
5.4
通讯作者：
Hu, Wei-Shau
中科院分区：
文献类型：
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作者：
Dilley, Kari A.;Nikolaitchik, Olga A.;Hu, Wei-Shau
大多数HIV-1病毒粒子包含两个全长病毒RNA拷贝，表明基因组包装是有效的和严格监管的。然而，结构蛋白GAG是组装非传染性病毒样颗粒所需的唯一成分，而病毒RNA在这一过程中是必不可少的。当病毒组装不需要可包装的病毒RNA时，允许HIV-1实现如此高效率的基因组包装的机制目前尚不清楚。在这份报告中，我们研究了HIV-1RNA在病毒组装中的作用，发现当GAG的表达水平与含有一个前病毒的细胞中的水平相似时，可包装的HIV-1RNA能够增强颗粒的产生。然而，当GAG过度表达时，这种增强作用就会减弱，这表明病毒RNA的作用可以被细胞中增加的GAG浓度所取代。我们还表明，GAG与病毒RNA之间的特异性相互作用是促进颗粒产生所必需的。综上所述，这些研究与我们之前的假设是一致的，即特定的二聚体病毒RNA-Gag相互作用是感染性病毒粒子组装的成核事件，确保每个新生病毒粒子中都有一个RNA二聚体。这些研究揭示了HIV-1在病毒组装过程中实现高效基因组包装的机制。重要的是，逆转录病毒组装是一个精心设计的事件，在这个过程中，许多病毒和细胞成分聚集在一起，产生具有感染性的病毒粒子。病毒RNA基因组携带遗传信息到新的宿主细胞，为产生新的病毒粒子提供指令，因此对病毒粒子的感染性是必不可少的。在这份报告中，我们证明了病毒RNA基因组与结构蛋白GAG的特异性相互作用促进了病毒粒子的组装和颗粒的产生。这些发现解决了一个难题，即HIV-1RNA被选择性地包装成高效率的病毒粒子，尽管对病毒粒子组装来说是必不可少的。了解HIV-1用来确保基因组打包的机制可以为病毒组装和复制提供重要的见解。
Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious viruslike particles, and the viral RNA is dispensable in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle production when Gag is expressed at levels similar to those in cells containing one provirus. However, such enhancement is diminished when Gag is overexpressed, suggesting that the effects of viral RNA can be replaced by increased Gag concentration in cells. We also showed that the specific interactions between Gag and viral RNA are required for the enhancement of particle production. Taken together, these studies are consistent with our previous hypothesis that specific dimeric viral RNA-Gag interactions are the nucleation event of infectious virion assembly, ensuring that one RNA dimer is packaged into each nascent virion. These studies shed light on the mechanism by which HIV-1 achieves efficient genome packaging during virus assembly.IMPORTANCE Retrovirus assembly is a well-choreographed event, during which many viral and cellular components come together to generate infectious virions. The viral RNA genome carries the genetic information to new host cells, providing instructions to generate new virions, and therefore is essential for virion infectivity. In this report, we show that the specific interaction of the viral RNA genome with the structural protein Gag facilitates virion assembly and particle production. These findings resolve the conundrum that HIV-1 RNA is selectively packaged into virions with high efficiency despite being dispensable for virion assembly. Understanding the mechanism used by HIV-1 to ensure genome packaging provides significant insights into viral assembly and replication.