Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin

PLoS Pathogens

Sunia A. Trauger¹  Giuseppe Destito¹  Marianne Manchester²  Kristopher J. Koudelka²  Emily M. Plummer²  Gary Siuzdak³ 

[1] Center for Integrative Molecular Biosciences, The Scripps Research Institute, La Jolla, California, United States of America;Department of Cell Biology, The Scripps Research Institute, La Jolla, California, United States of America;Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi Magna Graecia di Catanzaro, Viale Europa, Campus Universitario di Germaneto, Catanzaro, Italy

关键词: Vimentin;    Membrane proteins;    Cytoskeletal proteins;    Flow cytometry;    Cell membranes;    Aorta;    HeLa cells;    Antibodies;   

DOI  :  10.1371/journal.ppat.1000417

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.

【 授权许可】

CC BY