Department of Microbiology and Immunology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
Virology. 2010 Jun 20;402(1):11-9. doi: 10.1016/j.virol.2010.03.043. Epub 2010 Apr 20.
Adenovirus (Ad) membrane penetration during cell entry is poorly understood. Here we show that antibodies which neutralize the membrane lytic activity of the Ad capsid protein VI interfere with Ad endosomal membrane penetration. In vitro studies using a peptide corresponding to an N-terminal amphipathic alpha-helix of protein VI (VI-Phi), as well as other truncated forms of protein VI suggest that VI-Phi is largely responsible for protein VI binding to and lysing of membranes. Additional studies suggest that VI-Phi lies nearly parallel to the membrane surface. Protein VI fragments membranes and induces highly curved structures. Further studies suggest that protein VI induces positive membrane curvature. These data support a model in which protein VI binds membranes, inducing positive curvature strain which ultimately leads to membrane fragmentation. These results agree with previous observations of Ad membrane permeabilization during cell entry and provide an initial mechanistic description of a nonenveloped virus membrane lytic protein.
腺病毒（Ad）在细胞进入过程中的膜穿透机制尚不清楚。在这里，我们发现中和腺病毒衣壳蛋白 VI 的膜溶解活性的抗体干扰了 Ad 内体膜穿透。使用与蛋白 VI 的 N 端两性α螺旋（VI-Phi）相对应的肽以及其他截断形式的蛋白 VI 的体外研究表明，VI-Phi 在很大程度上负责蛋白 VI 与膜的结合和裂解。其他研究表明，VI-Phi 几乎与膜表面平行。蛋白 VI 裂解膜并诱导高度弯曲的结构。进一步的研究表明，蛋白 VI 诱导正膜曲率。这些数据支持这样一种模型，即蛋白 VI 结合膜，诱导正曲率应变，最终导致膜碎裂。这些结果与在细胞进入过程中观察到的 Ad 膜通透性一致，并为无包膜病毒膜溶解蛋白提供了初步的机制描述。
