Sanderson C M, Way M, Smith G L
Sir William Dunn School of Pathology, University of Oxford, United Kingdom.
J Virol. 1998 Feb;72(2):1235-43. doi: 10.1128/JVI.72.2.1235-1243.1998.
Many viruses induce profound changes in cell metabolism and function. Here we show that vaccinia virus induces two distinct forms of cell movement. Virus-induced cell migration was demonstrated by an in vitro wound healing assay in which infected cells migrated independently into the wound area while uninfected cells remained relatively static. Time-lapse microscopy showed that the maximal rate of migration occurred between 9 and 12 h postinfection. Virus-induced cell migration was inhibited by preinactivation of viral particles with trioxsalen and UV light or by the addition of cycloheximide but not by addition of cytosine arabinoside or rifampin. The expression of early viral genes is therefore necessary and sufficient to induce cell migration. Following migration, infected cells developed projections up to 160 microm in length which had growth-cone-like structures and were frequently branched. Time-lapse video microscopy showed that these projections were formed by extension and condensation of lamellipodia from the cell body. Formation of extensions was dependent on late gene expression but not the production of intracellular enveloped (IEV) particles. The requirements for virus-induced cell migration and for the formation of extensions therefore differ from each other and are distinct from the polymerization of actin tails on IEV particles. These data show that poxviruses encode genes which control different aspects of cell motility and thus represent a useful model system to study and dissect cell movement.
许多病毒会诱导细胞代谢和功能发生深刻变化。在此我们表明，痘苗病毒会诱导两种不同形式的细胞运动。通过体外伤口愈合试验证明了病毒诱导的细胞迁移，在该试验中，受感染细胞独立迁移到伤口区域，而未受感染细胞则保持相对静止。延时显微镜观察显示，迁移的最大速率发生在感染后9至12小时之间。病毒诱导的细胞迁移可通过用三甲沙林和紫外线对病毒颗粒进行预灭活或添加环己酰亚胺来抑制，但添加阿糖胞苷或利福平则不能抑制。因此，早期病毒基因的表达对于诱导细胞迁移是必要且充分的。迁移后，受感染细胞会形成长达160微米的突起，这些突起具有生长锥样结构且经常分支。延时视频显微镜观察显示，这些突起是由细胞体的片状伪足延伸和凝聚形成的。突起的形成依赖于晚期基因表达，但不依赖于细胞内包膜病毒粒子（IEV）的产生。因此，病毒诱导的细胞迁移和突起形成的要求彼此不同，且与IEV粒子上肌动蛋白尾的聚合不同。这些数据表明，痘病毒编码控制细胞运动不同方面的基因，因此是研究和剖析细胞运动的有用模型系统。
