Kao Sandra, Goila-Gaur Ritu, Miyagi Eri, Khan Mohammad A, Opi Sandrine, Takeuchi Hiroaki, Strebel Klaus
Laboratory of Molecular Microbiology, Viral Biochemistry Section, National Institute of Allergy and Infectious Diseases, NIH, Bldg. 4, Room 310, 4 Center Drive MSC 0460, Bethesda, MD 20892-0460, USA.
Virology. 2007 Dec 20;369(2):329-39. doi: 10.1016/j.virol.2007.08.005. Epub 2007 Sep 6.
HIV-1 Vif regulates viral infectivity by inhibiting the encapsidation of APOBEC3G (APO3G) through proteasomal degradation of the protein. Here we compared various Vif proteins for their ability to induce APO3G degradation and rescue viral infectivity. We found that Vif expressed from proviral vectors caused relatively inefficient degradation of APO3G in HeLa cells yet was very effective in inhibiting APO3G's antiviral activity. On the other hand, Vif expressed autonomously from a codon-optimized vector caused very efficient APO3G degradation and also effectively inhibited APO3G's antiviral effects. In contrast, a Vif chimera containing an N-terminal fluorescent tag efficiently induced APO3G degradation but was unable to restore viral infectivity. The lack of a direct correlation between APO3G degradation and rescue of viral infectivity suggests that these two properties of Vif are functionally separable. Our data imply that intracellular degradation of APO3G may not be the sole activity of Vif required for the production of infectious virions from APO3G-expressing cells.
HIV-1病毒感染因子（Vif）通过蛋白酶体降解APOBEC3G（APO3G）蛋白来抑制其包装，从而调节病毒的感染性。在此，我们比较了不同的Vif蛋白诱导APO3G降解以及恢复病毒感染性的能力。我们发现，前病毒载体表达的Vif在HeLa细胞中导致APO3G的降解效率相对较低，但在抑制APO3G的抗病毒活性方面却非常有效。另一方面，从密码子优化载体自主表达的Vif导致APO3G的高效降解，并且也有效地抑制了APO3G的抗病毒作用。相比之下，一个含有N端荧光标签的Vif嵌合体能够高效诱导APO3G降解，但无法恢复病毒感染性。APO3G降解与病毒感染性恢复之间缺乏直接相关性，这表明Vif的这两种特性在功能上是可分离的。我们的数据表明，APO3G的细胞内降解可能不是从表达APO3G的细胞产生有感染性病毒粒子所需的Vif的唯一活性。
