Capsid Protein VP4 of Human Rhinovirus Induces Membrane Permeability by the Formation of a Size-Selective Multimeric Pore

PLoS Pathogens

Sarah Gold¹  Tobias J. Tuthill¹  David J. Rowlands¹  Mike Strauss²  Nicola J. Stonehouse²  James M. Hogle²  James J. Chou³  Hannah Wenham³  Anusha Panjwani³  Terry Jackson³ 

[1] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America;School of Molecular and Cellular Biology & Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, West Yorkshire, United Kingdom;The Pirbright Institute, Pirbright, Surrey, United Kingdom

关键词: Permeability;    Liposomes;    Cell membranes;    Membrane characteristics;    Dextran;    Viral packaging;    Detergents;    Recombinant proteins;   

DOI  :  10.1371/journal.ppat.1004294

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Non-enveloped viruses must deliver their viral genome across a cell membrane without the advantage of membrane fusion. The mechanisms used to achieve this remain poorly understood. Human rhinovirus, a frequent cause of the common cold, is a non-enveloped virus of the picornavirus family, which includes other significant pathogens such as poliovirus and foot-and-mouth disease virus. During picornavirus cell entry, the small myristoylated capsid protein VP4 is released from the virus, interacts with the cell membrane and is implicated in the delivery of the viral RNA genome into the cytoplasm to initiate replication. In this study, we have produced recombinant C-terminal histidine-tagged human rhinovirus VP4 and shown it can induce membrane permeability in liposome model membranes. Dextran size-exclusion studies, chemical crosslinking and electron microscopy demonstrated that VP4 forms a multimeric membrane pore, with a channel size consistent with transfer of the single-stranded RNA genome. The membrane permeability induced by recombinant VP4 was influenced by pH and was comparable to permeability induced by infectious virions. These findings present a molecular mechanism for the involvement of VP4 in cell entry and provide a model system which will facilitate exploration of VP4 as a novel antiviral target for the picornavirus family.

【 授权许可】

CC BY