Khan M A, Aberham C, Kao S, Akari H, Gorelick R, Bour S, Strebel K
Laboratory of Molecular Microbiology, Viral Biochemistry Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892-0460, USA.
J Virol. 2001 Aug;75(16):7252-65. doi: 10.1128/JVI.75.16.7252-7265.2001.
The human immunodeficiency virus type 1 (HIV-1) Vif protein plays a critical role in the production of infectious virions. Previous studies have demonstrated the presence of small amounts of Vif in virus particles. However, Vif packaging was assumed to be nonspecific, and its functional significance has been questioned. We now report that packaging of Vif is dependent on the packaging of viral genomic RNA in both permissive and restrictive HIV-1 target cells. Mutations in the nucleocapsid zinc finger domains that abrogate packaging of viral genomic RNA abolished packaging of Vif. Additionally, an RNA packaging-defective virus exhibited significantly reduced packaging of Vif. Finally, deletion of a putative RNA-interacting domain in Vif abolished packaging of Vif into virions. Virion-associated Vif was resistant to detergent extraction and copurified with components of the viral nucleoprotein complex and functional reverse transcription complexes. Thus, Vif is specifically packaged into virions as a component of the viral nucleoprotein complex. Our data suggest that the specific association of Vif with the viral nucleoprotein complex might be functionally significant and could be a critical requirement for infectivity of viruses produced from restrictive host cells.
人类免疫缺陷病毒1型（HIV-1）的Vif蛋白在传染性病毒粒子的产生中起着关键作用。先前的研究已证明病毒粒子中存在少量Vif。然而，Vif的包装被认为是非特异性的，其功能意义也受到质疑。我们现在报告，在允许性和限制性HIV-1靶细胞中，Vif的包装均依赖于病毒基因组RNA的包装。核衣壳锌指结构域中的突变消除了病毒基因组RNA的包装，也消除了Vif的包装。此外，一种RNA包装缺陷型病毒的Vif包装显著减少。最后，Vif中一个假定的RNA相互作用结构域的缺失消除了Vif装入病毒粒子的过程。病毒粒子相关的Vif对去污剂提取具有抗性，并与病毒核蛋白复合物和功能性逆转录复合物的成分共纯化。因此，Vif作为病毒核蛋白复合物的一个组分被特异性地包装进病毒粒子。我们的数据表明，Vif与病毒核蛋白复合物的特异性结合可能具有功能意义，并且可能是从限制性宿主细胞产生的病毒感染性的关键要求。
