Identifying cellular genes crucial for the reactivation of Kaposi's sarcoma-associated herpesvirus latency
Identifying cellular genes crucial for the reactivation of Kaposi's sarcoma-associated herpesvirus latency
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DOI：
10.1099/vir.0.81603-0
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发表时间：
2006-03-01
影响因子：
3.8
通讯作者：
Akula, SM
中科院分区：
文献类型：
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作者：
Bryan, BA;Dyson, OF;Akula, SM
卡波济肉瘤相关疱疹病毒（KSHV）是人类疱疹病毒长名单上的最新成员。潜伏疱疹病毒感染的再激活仍然是一个谜。最近证明佛波醇酯TPA在诱导KSHV感染的细胞周期的S期的再活化中是有效的。在本研究中，流式细胞仪分选，TPA诱导，KSHV感染的造血细胞（BCBL-1）被用来分析癌症相关的细胞基因的表达谱在S期的细胞周期相比，GO/1期，通过使用微阵列。总的来说，细胞周期的S期似乎为KSHV提供了一个合适的环境，用于感染的生产性裂解周期。合适的条件包括促进存活性、DNA复制和脂质代谢的细胞信号传导，同时阻断细胞周期向M期的进展。与TPA诱导的BCBL-1细胞的GO/1期相比，在细胞周期的S期期间过表达的一些重要基因是v-myb成髓细胞瘤（MYBL 2）、蛋白激酶膜相关酪氨酸/苏氨酸1（PKMYT 1）、核糖核苷酸还原酶M1多肽（RRM 1）和过氧化物酶体增殖物激活受体δ（PPARD）。通过使用特异性短干扰RNA抑制PKMYT 1表达显著降低了TPA诱导的KSHV感染的裂解周期。这些基因和其他基因在KSHV再激活中的意义将在下面的报告中讨论。两者合计，流式细胞术芯片为基础的方法来研究细胞条件的KSHV感染的重新激活的关键是在这里首次报道。
Kaposi's sarcoma-associated herpesvirus (KSHV) is the latest addition to the long list of human herpesviruses. Reactivation of latent herpesvirus infections is still a mystery. It was demonstrated recently that the phorbol ester TPA was efficient in inducing a reactivation of KSHV infection in the S phase of the cell cycle. In the present study, flow cytometry-sorted, TPA-induced, KSHV-infected haematopoietic cells (BCBL-1) were used to analyse the expression profiles of cancer-related cellular genes in the S phase of the cell cycle compared with the GO/1 phase by using microarrays. Overall, the S phase of the cell cycle seems to provide KSHV with an apt environment for a productive lytic cycle of infection. The apt conditions include cellular signalling that promotes survivability, DNA replication and lipid metabolism, while blocking cell-cycle progression to M phase. Some of the important genes that were overexpressed during the S phase of the cell cycle compared with the GO/1 phase of TPA-induced BCBL-1 cells are v-myb myeloblastosis (MYBL2), protein kinase-membrane associated tyrosine/threonine 1 (PKMYT1), ribonucleotide reductase M1 polypeptide (RRM1) and peroxisome proliferator-activated receptors delta (PPARD). Inhibition of PKMYT1 expression by the use of specific short interfering RNAs significantly lowered the TPA-induced KSHV lytic cycle of infection. The significance of these and other genes in the reactivation of KSHV is discussed in the following report. Taken together, a flow cytometry-microarray-based method to study the cellular conditions critical for the reactivation of KSHV infection is reported here for the first time.