Olivares Isabel, Ballester Alicia, Lombardia Luis, Dominguez Orlando, López-Galíndez Cecilio
Servicio de Virología Molecular, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera de Pozuelo Km 2, Majadahonda, 28220 Madrid, Spain.
Virus Res. 2009 Jan;139(1):22-31. doi: 10.1016/j.virusres.2008.09.010. Epub 2008 Nov 25.
To investigate cellular factors involved in HIV-1 chronic infection, three cell lines chronically infected with the same HIV-1 viral isolate (s61) were studied by cDNA microarray analysis. Two T cell lines, H61 and M61, showed the characteristics of a persistent infection whereas U61 cell line displayed a latent infection pattern. Analysis of genes with altered expression in the three cell lines revealed evidence of apoptosis control by up-regulation of anti-apoptotic genes and down-regulation of pro-apoptotic genes. In addition, cell cycle control was affected in the two persistent T cell lines particularly through the down-regulation of cyclin-dependent kinase inhibitor 1A (CDKN1A/p21). Moreover, each cell line showed specific characteristics, like in M61 cells, genes related with cellular activation and with cell migration and motility. In U61 cells, genes associated with immune response were activated. Genes with altered expression in our experiments, and not previously related with HIV such as ANXA 1 or CFLAR were detected and validated. This work revealed that different cell mechanism such as control of apoptosis and cell cycle are important for "in vitro" HIV-1 chronic infections, and discovered new genes previously not related with HIV-1 replication.
为了研究参与HIV-1慢性感染的细胞因子,通过cDNA微阵列分析对三种被同一HIV-1病毒分离株(s61)慢性感染的细胞系进行了研究。两种T细胞系H61和M61表现出持续感染的特征,而U61细胞系呈现潜伏感染模式。对这三种细胞系中表达改变的基因进行分析,发现了通过上调抗凋亡基因和下调促凋亡基因来控制细胞凋亡的证据。此外,细胞周期调控在两种持续感染的T细胞系中受到影响,特别是通过细胞周期蛋白依赖性激酶抑制剂1A(CDKN1A/p21)的下调。此外,每个细胞系都表现出特定的特征,如在M61细胞中,有与细胞活化以及细胞迁移和运动相关的基因。在U61细胞中,与免疫反应相关的基因被激活。在我们的实验中检测并验证了表达改变且以前与HIV无关的基因,如膜联蛋白A1(ANXA 1)或含半胱氨酸的天冬氨酸蛋白水解酶抑制蛋白(CFLAR)。这项工作表明,诸如细胞凋亡控制和细胞周期调控等不同的细胞机制对“体外”HIV-1慢性感染很重要,并发现了以前与HIV-1复制无关的新基因。