Department of Microbiology, Penn Genome Frontiers Institute, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
PLoS Pathog. 2010 Jun 17;6(6):e1000954. doi: 10.1371/journal.ppat.1000954.
Poxviruses include medically important human pathogens, yet little is known about the specific cellular factors essential for their replication. To identify genes essential for poxvirus infection, we used high-throughput RNA interference to screen the Drosophila kinome for factors required for vaccinia infection. We identified seven genes including the three subunits of AMPK as promoting vaccinia infection. AMPK not only facilitated infection in insect cells, but also in mammalian cells. Moreover, we found that AMPK is required for macropinocytosis, a major endocytic entry pathway for vaccinia. Furthermore, we show that AMPK contributes to other virus-independent actin-dependent processes including lamellipodia formation and wound healing, independent of the known AMPK activators LKB1 and CaMKK. Therefore, AMPK plays a highly conserved role in poxvirus infection and actin dynamics independent of its role as an energy regulator.
痘病毒包括一些重要的医学病原体，但对于其复制所必需的特定细胞因子却知之甚少。为了鉴定痘病毒感染所必需的基因，我们使用高通量 RNA 干扰筛选了果蝇激酶组中对痘苗病毒感染必需的因子。我们鉴定了七个基因，包括 AMPK 的三个亚基，它们促进了牛痘病毒的感染。AMPK 不仅促进了昆虫细胞的感染，也促进了哺乳动物细胞的感染。此外，我们发现 AMPK 是巨胞饮作用所必需的，巨胞饮作用是牛痘病毒的主要内吞进入途径。此外，我们还表明，AMPK 有助于其他与病毒无关的肌动蛋白依赖性过程，包括片状伪足形成和伤口愈合，而不依赖于已知的 AMPK 激活剂 LKB1 和 CaMKK。因此，AMPK 在痘病毒感染和肌动蛋白动力学中发挥着高度保守的作用，而不依赖于其作为能量调节剂的作用。
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