Department of Hematology/Oncology and Infectious Diseases, Johann Wolfgang Goethe University Hospital, Frankfurt/Main, Germany.
Intervirology. 2012;55(4):263-75. doi: 10.1159/000328323. Epub 2011 Aug 25.
To unravel the interplay between HIV-1 and its host cell, the effect of HIV-1 infection on cellular gene expression was investigated.
HIV-1(SF33)-infected and uninfected H9 T cells were screened by differential display and RNase protection assay. The finding (PDS5A) was confirmed in HIV-1(Lai)-infected P4-CCR5 HeLa cells, which were also examined after PDS5A siRNA knockdown in regard to HIV-1 replication by quantitative RT-PCR, p24 ELISA and LTR-driven β-galactosidase expression. The PDS5A knockdown effect on cellular gene expressions was studied by microarray analysis. PDS5A tissue expression was determined by Northern blotting.
Regulator of cohesion maintenance, homolog A (PDS5A) was found to be down-regulated by HIV-1. When PDS5A was suppressed by siRNA, HIV-1 replication was unaffected. PDS5A was found to be highly expressed in skeletal muscle tissue, and to lesser degrees in pancreas, heart, placenta, lung, kidney, liver and brain. Microarray analysis of PDS5A knockdown revealed 91 differential gene products over-representing cell cycle, transport and protein stability regulation, including 4 genes (PP2A, RANTES, PCAF, TCF7L2) previously reported to interact with HIV-1.
The data show a downregulation of proliferation-associated host gene PDS5A and suggest a role of PDS5A in HIV-1-induced cellular pathogenesis but not viral replication.
揭示 HIV-1 与其宿主细胞之间的相互作用，研究 HIV-1 感染对细胞基因表达的影响。
通过差异显示和 RNase 保护分析筛选出受 HIV-1 感染和未感染的 H9 T 细胞。在 HIV-1(Lai)感染的 P4-CCR5 HeLa 细胞中证实了这一发现（PDS5A），并在 PDS5A siRNA 敲低后，通过定量 RT-PCR、p24 ELISA 和 LTR 驱动的β-半乳糖苷酶表达来检查 HIV-1 复制情况。通过微阵列分析研究 PDS5A 敲低对细胞基因表达的影响。通过 Northern 印迹确定 PDS5A 的组织表达。
发现维持凝聚调节因子同源物 A（PDS5A）被 HIV-1 下调。当 PDS5A 被 siRNA 抑制时，HIV-1 复制不受影响。PDS5A 在骨骼肌组织中高度表达，在胰腺、心脏、胎盘、肺、肾、肝和脑组织中表达程度较低。PDS5A 敲低的微阵列分析显示，有 91 个差异基因产物过度表达，涉及细胞周期、运输和蛋白质稳定性调节，包括 4 个先前报道与 HIV-1 相互作用的基因（PP2A、RANTES、PCAF、TCF7L2）。
数据显示与增殖相关的宿主基因 PDS5A 下调，并提示 PDS5A 在 HIV-1 诱导的细胞发病机制中起作用，但不是病毒复制。
