Magnuson Brian, Rainey Emily K, Benjamin Thomas, Baryshev Mikhail, Mkrtchian Souren, Tsai Billy
Department of Cell and Developmental Biology, University of Michigan Medical School, 4643 Medical Sciences II, 1335 East Catherine Street, Ann Arbor, Michigan 48109, USA.
Mol Cell. 2005 Oct 28;20(2):289-300. doi: 10.1016/j.molcel.2005.08.034.
Membrane penetration of nonenveloped viruses is a poorly understood process. We have investigated early stages of this process by studying the conformational change experienced by polyomavirus (Py) in the lumen of the endoplasmic reticulum (ER), a step that precedes its transport into the cytosol. We show that a PDI-like protein, ERp29, exposes the C-terminal arm of Py's VP1 protein, leading to formation of a hydrophobic particle that binds to a lipid bilayer; this reaction likely mimics initiation of Py penetration across the ER membrane. Expression of a dominant-negative ERp29 decreases Py infection, indicating ERp29 facilitates viral infection. Interestingly, cholera toxin, another toxic agent that crosses the ER membrane into the cytosol, is unfolded by PDI in the ER. Our data thus identify an ER factor that mediates membrane penetration of a nonenveloped virus and suggest that PDI family members are generally involved in ER remodeling reactions.
无包膜病毒的膜穿透过程是一个尚未被充分理解的过程。我们通过研究多瘤病毒（Py）在内质网（ER）腔内经历的构象变化来探究这一过程的早期阶段，这是其转运到细胞质之前的一个步骤。我们发现一种类PDI蛋白ERp29会暴露Py的VP1蛋白的C末端臂，导致形成一个与脂质双层结合的疏水颗粒；该反应可能模拟了Py穿过ER膜的起始过程。显性负性ERp29的表达会降低Py感染，表明ERp29促进病毒感染。有趣的是，另一种穿过ER膜进入细胞质的毒性因子霍乱毒素在ER中被PDI展开。因此，我们的数据鉴定出一种介导无包膜病毒膜穿透的ER因子，并表明PDI家族成员通常参与ER重塑反应。
