Characterization of human immunodeficiency virus type 1 Vif particle incorporation

Characterization of human immunodeficiency virus type 1 Vif particle incorporation
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DOI:
10.1128/jvi.70.9.6106-6111.1996
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发表时间:
1996-09-01
影响因子:
5.4
通讯作者:
Trono, D
Trono, D
中科院分区:
医学2区
文献类型:
--
作者:
Camaur, D;Trono, D

文献摘要

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人类免疫缺陷病毒1型(HIV-1)Vif蛋白在病毒颗粒形成时是必需的,但在病毒粒子进入靶细胞后在功能上表现出其作用。这表明Vif要么作用于另一种病毒蛋白质,要么本身被掺入颗粒中。在本研究中,我们研究了后一种可能性。我们证实了我们以前的观察,Vif被纳入人类免疫缺陷病毒1型病毒粒子的比例约为1分子的Vif每75至220分子的p24,或7至20分子的病毒粒子。此外,我们证明了Vif的相对浓度在颗粒中比在感染的细胞中低得多,而对于主要的病毒组分观察到相反的情况。病毒包膜、Nef、Vpr、Vpu、蛋白酶、逆转录酶、整合酶、核衣壳和p6(gag)蛋白以及病毒基因组RNA被包装用于Vif包装。此外,突变Vif的几个高度保守的残基(H-108、C-114、C-133、L-145和Q-146)或缺失Vif的C-末端18个氨基酸(这两种突变都严重损害Vif功能)都不能消除Vif掺入病毒体。最后,Vif可以包装到小鼠白血病病毒颗粒中。基于这些数据,我们得出结论,Vif纳入病毒体的特异性仍然是一个悬而未决的问题。
The human immunodeficiency virus type 1 (HIV-1) Vif protein is necessary at the time of viral particle formation yet functionally manifests its effect after virions enter target cells. This suggests that Vif either acts on another viral protein or is itself incorporated into particles. In this study, we have examined the latter possibility. We confirm our previous observation that Vif is incorporated into human immunodeficiency virus type 1 virions at a ratio of approximately 1 molecule of Vif for every 75 to 220 molecules of p24, or 7 to 20 molecules per virion. Furthermore, we demonstrate that the relative concentration of Vif is much lower in particles than in infected cells, whereas the opposite is observed for the main virus components. The viral envelope, Nef, Vpr, Vpu, protease, reverse transcriptase, integrase, nucleocapsid, and p6(gag) proteins as well as the viral genomic RNA, are dispensable for Vif packaging. Furthermore, mutating several highly conserved residues (H-108, C-114, C-133, L-145, and Q-146) or deleting the C-terminal 18 amino acids of Vif, either of which severely impairs Vif function, does not abolish its incorporation into virions. Finally, Vif can be packaged into murine leukemia virus particles. On the basis of these data, we conclude that the specificity of Vif incorporation into virions remains an open question.