Production of infectious virus and degradation of APOBEC3G are separable functional properties of human immunodeficiency virus type 1 Vif

Production of infectious virus and degradation of APOBEC3G are separable functional properties of human immunodeficiency virus type 1 Vif
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DOI:
10.1016/j.virol.2007.08.005
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发表时间:
2007-12-20
期刊:
影响因子:
3.7
通讯作者:
Strebel, Klaus
Strebel, Klaus
中科院分区:
医学3区
文献类型:
--
作者:
Kao, Sandra;Goila-Gaur, Ritu;Strebel, Klaus

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HIV-1 Vif通过蛋白酶体降解APOBEC 3G(APO 3G)来抑制APOBEC 3G的糖苷化,从而调节病毒感染性。在这里,我们比较了各种Vif蛋白诱导APO 3G降解和拯救病毒感染性的能力。我们发现,Vif表达的前病毒载体造成相对低效的降解载脂蛋白3G在HeLa细胞中,但在抑制载脂蛋白3G的抗病毒活性是非常有效的。另一方面,从密码子优化的载体中自主表达的Vif引起非常有效的APO 3G降解,并有效地抑制APO 3G的抗病毒作用。相反,含有N-末端荧光标记的Vif嵌合体有效诱导APO 3G降解,但不能恢复病毒感染性。APO 3G降解和拯救病毒感染性之间缺乏直接相关性表明Vif的这两种性质在功能上是可分离的。我们的数据意味着APO 3G的细胞内降解可能不是从表达APO 3G的细胞中产生感染性病毒粒子所需的Vif的唯一活性。爱思唯尔公司出版
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. Published by Elsevier Inc.