Role of human cytomegalovirus immediate-early proteins in cell growth control
Role of human cytomegalovirus immediate-early proteins in cell growth control
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DOI：
10.1128/jvi.74.17.8028-8037.2000
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发表时间：
2000-09-01
影响因子：
5.4
通讯作者：
Kowalik, TF
中科院分区：
文献类型：
--
作者：
Castillo, JP;Yurochko, AD;Kowalik, TF
人类巨细胞病毒（HCMV）是一种普遍存在的疱疹病毒，与多种疾病有关，包括在再狭窄中观察到的HCMV再激活与动脉平滑肌细胞过度增殖之间的关联。虽然HCMV可以在感染细胞中介导生长抑制表型，但病毒也可以促进有利于增殖的环境。在这里，我们提供的证据表明，HCMV即时早期（IE）蛋白IE1-72和IE2-86可能通过改变细胞周期控制来诱导这种增殖环境。我们发现这两种IE蛋白的表达都可以改变随机循环细胞向S期和G(2)/M期的细胞周期分布。此外，我们发现IE2-86而非IE1-72的表达可诱导静止细胞进入S期并延迟细胞周期退出。在p53缺失的情况下，IE1-72表达可诱导S期，延迟细胞周期退出。我们还证明，在IE1-72表达后，成纤维细胞中p53蛋白水平升高。表达IE1-72的细胞中p53蛋白的积累可能是IE1-72无法诱导S期和延迟细胞周期退出的原因。我们的数据表明，HCMV IE1-72和IE2-86的表达足以改变细胞周期，从而产生有利于增殖的环境。
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that has been implicated in several disorders, including an association between HCMV reactivation and the overproliferation of arterial smooth muscle cells observed in restenosis. Although HCMV can mediate a growth-arrest phenotype in infected cells, the virus can also promote an environment conducive to proliferation. Here, we present evidence that the HCMV immediate-early (IE) proteins, IE1-72 and IE2-86, may be responsible for inducing this proliferative environment by altering cell cycle control. We find that expression of either of these IE proteins can alter the cell cycle distribution of randomly cycling cells towards S and G(2)/M phases. Additionally, we find that expression of IE2-86, but not IE1-72, induces quiescent cells into S phase and delays cell cycle exit. In the absence of p53, IE1-72 expression can induce S phase and delay cell cycle exit. We also demonstrate that p53 protein levels increase in fibroblasts following the expression of IE1-72. The observed accumulation of p53 protein in IE1-72-expressing cells may account for the inability of IE1-72 to induce S phase and delay cell cycle exit. Our data suggest that expression of HCMV IE1-72 and IE2-86 is sufficient to alter the cell cycle to generate an environment conducive to proliferation.