Friend virus utilizes the BMP4-dependent stress erythropoiesis pathway to induce erythroleukemia.
Friend virus utilizes the BMP4-dependent stress erythropoiesis pathway to induce erythroleukemia.
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Friend病毒利用BMP4依赖性应激红细胞生成途径诱发红白血病。
DOI：
10.1128/jvi.02487-06
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发表时间：
2008
影响因子：
5.4
通讯作者：
Paulson,RobertF
中科院分区：
文献类型：
--
作者：
Subramanian,Aparna;Hegde,Shailaja;Porayette,Prashanth;Yon,Michele;Hankey,Pamela;Paulson,RobertF
50多年的遗传分析已经确定了一些宿主基因，这些基因是在friend病毒诱导的红细胞白血病进展过程中被感染细胞扩增所必需的。在本报告中，我们发现Friend病毒在脾脏中诱导骨形态发生蛋白4 （bone morphogenetic protein 4, BMP4）依赖的应激性红细胞生成途径，迅速扩增靶细胞，传播其感染并导致急性脾肿大。这种机制模拟了对急性贫血的反应，在急性贫血中，脾脏中表达的BMP4驱动应激红细胞祖细胞的特化群体的扩张。先前我们证实这些被称为应激BFU-E的祖细胞是脾脏Friend病毒的靶标（A. Subramanian， H. E. Teal， P. H. Correll， R. F. Paulson， J. Virol.79:14586-14594, 2005）。在这里，我们通过显示Friend病毒感染两种不同的骨髓细胞群来扩展这些发现。一个群体在感染后，以不依赖于epo的方式分化为成熟红细胞，而另一个群体在感染后迁移到脾脏，在那里诱导BMP4表达并充当病毒库。Friend病毒激活脾脏应激性红细胞生成途径，导致应激BFU-E迅速扩增，为病毒感染提供了丰富的靶细胞。这些观察结果提示了一种新的机制，即病毒通过诱导应激反应途径放大病毒的靶细胞，导致受感染细胞的急性扩增。
More than 50 years of genetic analysis has identified a number of host genes that are required for the expansion of infected cells during the progression of Friend-virus-induced erythroleukemia. In this report, we show that Friend virus induces the bone morphogenetic protein 4 (BMP4)-dependent stress erythropoiesis pathway in the spleen, which rapidly amplifies target cells, propagating their infection and resulting in acute splenomegaly. This mechanism mimics the response to acute anemia, in which BMP4 expressed in the spleen drives the expansion of a specialized population of stress erythroid progenitors. Previously we demonstrated that these progenitors, termed stress BFU-E, are targets for Friend virus in the spleen (A. Subramanian, H. E. Teal, P. H. Correll, and R. F. Paulson, J. Virol.79:14586-14594, 2005). Here, we extend those findings by showing that Friend virus infects two distinct populations of bone marrow cells. One population, when infected, differentiates into mature erythrocytes in an Epo-independent manner, while a second population migrates to the spleen after infection, where it induces BMP4 expression and acts as a reservoir of virus. The activation of the stress erythropoiesis pathway in the spleen by Friend virus results in the rapid expansion of stress BFU-E, providing abundant target cells for viral infection. These observations suggest a novel mechanism by which a virus induces a stress response pathway that amplifies target cells for the virus, leading to acute expansion of infected cells.