Vallanti Giuliana, Lupo Rossella, Federico Maurizio, Mavilio Fulvio, Bovolenta Chiara
Molmed SpA, Milan, Italy.
Mol Ther. 2005 Oct;12(4):697-706. doi: 10.1016/j.ymthe.2005.05.014.
The viral infectivity factor (Vif) is an essential component of the HIV-1 infectious cycle. Vif counteracts the action of the cytidine deaminase APOBEC3G (AP3G), which confers nonimmune antiviral defense against HIV-1 to T lymphocytes. Disabling or interfering with the function of Vif could represent an alternative therapeutic approach to AIDS. We have expressed a natural mutant of Vif, F12-Vif, in a VSV-G-pseudotyped lentiviral vector under the Tat-inducible control of the HIV-1 LTR. Conditional expression of F12-Vif prevents replication and spreading of both CXCR4 and CCR5 strains of HIV-1 in human primary T lymphocyte and T cell lines. T cells transduced with F12-Vif release few HIV-1 virions and with reduced infectivity. Several lines of evidence indicate that HIV-1 interference requires the presence of both wild-type and F12-Vif proteins, suggesting a dominant-negative feature of the F12-Vif mutant. Surprisingly, however, the F12-Vif-mediated inhibition does not depend on the reestablishment of the AP3G function.
病毒感染性因子（Vif）是HIV-1感染周期的一个重要组成部分。Vif可抵消胞苷脱氨酶载脂蛋白B mRNA编辑酶催化多肽样3G（APOBEC3G，AP3G）的作用，AP3G赋予T淋巴细胞对HIV-1的非免疫抗病毒防御能力。使Vif功能失活或受到干扰可能代表一种治疗艾滋病的替代方法。我们在HIV-1长末端重复序列（LTR）的Tat诱导控制下，在水疱性口炎病毒糖蛋白（VSV-G）假型慢病毒载体中表达了Vif的一种天然突变体F12-Vif。F12-Vif的条件性表达可阻止HIV-1的CXCR4和CCR5毒株在人原代T淋巴细胞和T细胞系中的复制和传播。用F12-Vif转导的T细胞释放的HIV-1病毒粒子很少且感染性降低。多项证据表明，HIV-1干扰需要野生型和F12-Vif蛋白同时存在，这表明F12-Vif突变体具有显性负性特征。然而，令人惊讶的是，F12-Vif介导的抑制作用并不依赖于AP3G功能的重建。
