Cellular gene expression upon human immunodeficiency virus type 1 infection of CD4+-T-cell lines
Cellular gene expression upon human immunodeficiency virus type 1 infection of CD4+-T-cell lines
复制标题
DOI：
10.1128/jvi.77.2.1392-1402.2003
复制
发表时间：
2003-01-01
影响因子：
5.4
通讯作者：
Mullins, JI
中科院分区：
文献类型：
--
作者：
van't Wout, AB;Lehrman, GK;Mullins, JI
应用DNA微阵列技术检测了人类免疫缺陷病毒1型BRU株（HIV-1（BRU））感染后不同时间CD 4（+）-T细胞系中约4,600个细胞RNA转录本的表达水平。我们发现，几类基因被HIV-1（BRU）感染抑制，与Vpr诱导的HIV-1感染细胞的G，逮捕一致。这些基因包括参与细胞分裂和转录的基因，一个死亡盒蛋白（RNA解旋酶）家族，以及所有参与翻译和剪接的基因。然而，在感染的细胞中细胞活化和信号传导的总体水平增加，与强病毒产生一致。这些包括转录因子的亚组，包括EGR 1和JUN，表明它们在HIV-1生命周期中发挥特定作用。一些调节变化是细胞系特异性的;然而，大多数变化，包括参与胆固醇生物合成的酶，在大多数感染的细胞系中受到调节。将我们的HIV-1感染实验的基因表达谱与暴露于热休克、干扰素或甲型流感病毒的细胞的基因表达谱进行比较的纲要分析表明，HIV-1感染在很大程度上诱导了特异性变化，而不是简单地激活应激反应或细胞因子反应途径。因此，微阵列分析证实了几种已知的HIV-1宿主细胞相互作用，并允许识别以前未涉及HIV-1感染的特定细胞途径。预计持续的分析将提出通过靶向这些途径影响体内HIV-1复制的策略。
The expression levels of similar to4,600 cellular RNA transcripts were assessed in CD4(+)-T-cell lines at different times after infection with human immunodeficiency virus type 1 strain BRU (HIV-1(BRU)) using DNA microarrays. We found that several classes of genes were inhibited by HIV-1(BRU) infection, consistent with the G, arrest of HIV-1-infected cells induced by Vpr. These included genes involved in cell division and transcription, a family of DEAD-box proteins (RNA helicases), and all genes involved in translation and splicing. However, the overall level of cell activation and signaling was increased in infected cells, consistent with strong virus production. These included a subgroup of transcription factors, including EGR1 and JUN, suggesting they play a specific role in the HIV-1 life cycle. Some regulatory changes were cell line specific; however, the majority, including enzymes involved in cholesterol biosynthesis, of changes were regulated in most infected cell lines. Compendium analysis comparing gene expression profiles of our HIV-1 infection experiments to those of cells exposed to heat shock, interferon, or influenza A virus indicated that HIV-1 infection largely induced specific changes rather than simply activating stress response or cytokine response pathways. Thus, microarray analysis confirmed several known HIV-1 host cell interactions and permitted identification of specific cellular pathways not previously implicated in HIV-1 infection. Continuing analyses are expected to suggest strategies for impacting HIV-1 replication in vivo by targeting these pathways.