Manuilova E S, Arsenyeva E L, Khaidarova N V, Shugurova I M, Inozemtseva L S, Tarantul V Z, Grivennikov I A
Department of Viral and Cellular Molecular Genetics, Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia.
Int J Biomed Sci. 2008 Mar;4(1):29-37.
To examine the effects of the tat and nef regulatory genes of human immunodeficiency virus (HIV-1) on cell differentiation we used the mouse embryonic stem cells (ESC) as a model. Proliferation, embryoid bodies (EB) formation and subsequent differentiation into cardiomyocytes, glial and neuronal cells were investigated in ESC lines transfected with these genes. It has been shown that the transfection of ESC by the tat gene increased their proliferating activity, whereas the nef gene transfected ESC showed its decrease. The number of embryoid bodies formed was higher in the cultures of ESC transfected by the nef and lower in the cells transfected by the tat in comparison with controls. The percentage of embryoid bodies with contracting cardiomyocytes was higher against control in the nef transfected cells and lower in ESC transfected with the tat. There were no reliable differences in the appearance of glial cells between control and the nef and tat transfected cell lines. Spontaneous differentiation of ESC into neuronal cells was almost not observed in the nef transfected cells, in contrast to control and the tat transfected cells. However, addition of retinoic acid (RA) to the nef transfected cells caused even a slight increase in neuron formation as compared to control ESC treated with RA. Thus, for the first time we have shown that the tat and nef regulatory genes of HIV-1 had a visible effect on proliferation of ESC and some first steps of their differentiation. In general, the reverse correlation between the effects of these two viral genes on ESC proliferation and differentiation were observed.
为了研究人类免疫缺陷病毒（HIV-1）的tat和nef调控基因对细胞分化的影响，我们以小鼠胚胎干细胞（ESC）为模型。在转染了这些基因的ESC系中，研究了细胞增殖、胚状体（EB）形成以及随后向心肌细胞、神经胶质细胞和神经元细胞的分化情况。结果表明，tat基因转染ESC可增加其增殖活性，而nef基因转染ESC则使其增殖活性降低。与对照组相比，nef转染ESC培养物中形成的胚状体数量更多，而tat转染细胞中形成的胚状体数量更少。nef转染细胞中具有收缩性心肌细胞的胚状体百分比相对于对照组更高，而tat转染ESC中则更低。在对照组与nef和tat转染细胞系之间，神经胶质细胞的出现没有可靠差异。与对照组和tat转染细胞不同，nef转染细胞中几乎未观察到ESC自发分化为神经元细胞。然而，与用视黄酸（RA）处理的对照ESC相比，向nef转染细胞中添加RA甚至使神经元形成略有增加。因此，我们首次表明HIV-1的tat和nef调控基因对ESC的增殖及其分化的一些初始步骤有明显影响。总体而言，观察到这两个病毒基因对ESC增殖和分化的影响呈负相关。
