Structure of the Immature Dengue Virus at Low pH Primes Proteolytic Maturation

作者：I-Mei Yu, Wei Zhang, Heather A. Holdaway, Long Li, V.A. Kostyuchenko, Paul R. Chipman, Richard Kühn, Michael G. Rossmann, Jue Chen · 发表于：Science · 年份：2008 · DOI：10.1126/science.1153264 · 被引用次数：626 · 研究领域：Mosquito-borne diseases and control、Invertebrate Immune Response Mechanisms、Vibrio bacteria research studies

Intracellular cleavage of immature flaviviruses is a critical step in assembly that generates the membrane fusion potential of the E glycoprotein. With cryo-electron microscopy we show that the immature dengue particles undergo a reversible conformational change at low pH that renders them accessible to furin cleavage. At a pH of 6.0, the E proteins are arranged in a herringbone pattern with the pr peptides docked onto the fusion loops, a configuration similar to that of the mature virion. After cleavage, the dissociation of pr is pH-dependent, suggesting that in the acidic environment of the trans-Golgi network pr is retained on the virion to prevent membrane fusion. These results suggest a mechanism by which flaviviruses are processed and stabilized in the host cell secretory pathway.