Gill Michael B, Edgar Rachel, May Janet S, Stevenson Philip G
Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
PLoS One. 2008 Mar 19;3(3):e1808. doi: 10.1371/journal.pone.0001808.
Viruses lack self-propulsion. To move in multi-cellular hosts they must therefore manipulate infected cells. Herpesviruses provide an archetype for many aspects of host manipulation, but only for alpha-herpesviruses in is there much information about they move. Other herpesviruses are not necessarily the same. Here we show that Murine gamma-herpesvirus-68 (MHV-68) induces the outgrowth of long, branched plasma membrane fronds to create an intercellular network for virion traffic. The fronds were actin-based and RhoA-dependent. Time-lapse imaging showed that the infected cell surface became highly motile and that virions moved on the fronds. This plasma membrane remodelling was driven by the cytoplasmic tail of gp48, a MHV-68 glycoprotein previously implicated in intercellular viral spread. The MHV-68 ORF58 was also required, but its role was simply transporting gp48 to the plasma membrane, since a gp48 mutant exported without ORF58 did not require ORF58 to form membrane fronds either. Together, gp48/ORF58 were sufficient to induce fronds in transfected cells, as were the homologous BDLF2/BMRF2 of Epstein-Barr virus. Gp48/ORF58 therefore represents a conserved module by which gamma-herpesviruses rearrange cellular actin to increase intercellular contacts and thereby promote their spread.
病毒缺乏自我推进能力。因此，在多细胞宿主体内移动时，它们必须操控被感染的细胞。疱疹病毒在宿主操控的许多方面提供了一个原型，但只有关于α - 疱疹病毒如何移动有较多信息。其他疱疹病毒情况未必相同。在此我们表明，小鼠γ - 疱疹病毒68（MHV - 68）诱导长的、分支状的质膜叶状突起生长，以形成用于病毒粒子运输的细胞间网络。这些叶状突起基于肌动蛋白且依赖RhoA。延时成像显示，被感染的细胞表面具有高度的运动性，并且病毒粒子在叶状突起上移动。这种质膜重塑是由gp48的细胞质尾巴驱动的，gp48是一种先前与细胞间病毒传播有关的MHV - 68糖蛋白。MHV - 68的ORF58也是必需的，但其作用仅仅是将gp48转运到质膜，因为一个没有ORF58而输出的gp48突变体形成膜叶状突起也不需要ORF58。总之，gp48/ORF58足以在转染细胞中诱导叶状突起，爱泼斯坦 - 巴尔病毒的同源物BDLF2/BMRF2也是如此。因此，gp48/ORF58代表了一个保守的模块，γ - 疱疹病毒通过该模块重新排列细胞肌动蛋白以增加细胞间接触，从而促进其传播。
