Structural Correlates of Rotavirus Cell Entry

PLoS Pathogens

Eric N. Salgado¹  Stephen C. Harrison¹  Aliaa H. Abdelhakim¹  Tomas Kirchhausen²  Mithun Pasham²  Daniela Nicastro³  Xiaofeng Fu³ 

[1] Laboratory of Molecular Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America;Program in Cellular and Molecular Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America;Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts, United States of America

关键词: Rotavirus infection;    Virions;    Cell membranes;    Vesicles;    Cytosol;    Antibodies;    Electron microscopy;    Rotavirus;   

DOI  :  10.1371/journal.ppat.1004355

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Cell entry by non-enveloped viruses requires translocation into the cytosol of a macromolecular complex—for double-strand RNA viruses, a complete subviral particle. We have used live-cell fluorescence imaging to follow rotavirus entry and penetration into the cytosol of its ∼700 Å inner capsid particle (“double-layered particle”, DLP). We label with distinct fluorescent tags the DLP and each of the two outer-layer proteins and track the fates of each species as the particles bind and enter BSC-1 cells. Virions attach to their glycolipid receptors in the host cell membrane and rapidly become inaccessible to externally added agents; most particles that release their DLP into the cytosol have done so by ∼10 minutes, as detected by rapid diffusional motion of the DLP away from residual outer-layer proteins. Electron microscopy shows images of particles at various stages of engulfment into tightly fitting membrane invaginations, consistent with the interpretation that rotavirus particles drive their own uptake. Electron cryotomography of membrane-bound virions also shows closely wrapped membrane. Combined with high resolution structural information about the viral components, these observations suggest a molecular model for membrane disruption and DLP penetration.

【 授权许可】

CC BY