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Human Immunodeficiency Virus Type 1 Vif Is Efficiently Packaged into Virions during Productive but Not Chronic Infection

机译:1型人类免疫缺陷病毒Vif在生产性感染而非慢性感染期间被有效地包装到病毒颗粒中

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摘要

Packaging of the human immunodeficiency virus type 1 Vif protein into virus particles is mediated through an interaction with viral genomic RNA and results in the association of Vif with the nucleoprotein complex. Despite the specificity of this process, calculations of the amount of Vif packaged have produced vastly different results. Here, we compared the efficiency of packaging of Vif into virions derived from acutely and chronically infected H9 cells. We found that Vif was efficiently packaged into virions from acutely infected cells (60 to 100 copies per virion), while packaging into virions from chronically infected H9 cells was near the limit of detection (four to six copies of Vif per virion). Superinfection by an exogenous Vif-defective virus did not rescue packaging of endogenous Vif expressed in the chronically infected culture. In contrast, exogenous Vif expressed by superinfection of wild-type virus was readily packaged (30 to 40 copies per virion). Biochemical analyses suggest that the differences in the relative packaging efficiencies were not due to gross differences in the steady-state distribution of Vif in chronically or acutely infected cells but are likely due to differences in the relative rates of de novo synthesis of Vif. Despite its low packaging efficiency, endogenously expressed Vif was sufficient to direct the production of viruses with almost wild-type infectivity. The results from our study provide novel insights into the biochemical properties of Vif and offer an explanation for the reported differences regarding Vif packaging.
机译:通过与病毒基因组RNA的相互作用将人免疫缺陷病毒1型Vif蛋白包装到病毒颗粒中,并导致Vif与核蛋白复合物缔合。尽管此过程具有特殊性,但Vif包装量的计算却产生了截然不同的结果。在这里,我们比较了将Vif包装到来源于急性和慢性感染H9细胞的病毒粒子中的效率。我们发现Vif可有效地从急性感染的细胞中包装到病毒体中(每个病毒体60至100拷贝),而从慢性感染的H9细胞中包装到病毒体中则接近检测极限(每个病毒体4至6拷贝Vif)。外源性Vif缺陷病毒的过度感染不能挽救在慢性感染培养物中表达的内源性Vif的包装。相反,通过野生型病毒的超感染表达的外源Vif易于包装(每个病毒体30至40拷贝)。生化分析表明,相对包装效率的差异并非归因于慢性或急性感染细胞中Vif稳态分布的总体差异,而可能归因于Vif从头合成的相对速率差异。尽管包装效率低,但是内源表达的Vif足以指导几乎具有野生型感染性的病毒生产。我们研究的结果为Vif的生化特性提供了新颖的见解,并为所报道的Vif包装差异提供了解释。

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