Endoplasmic reticulum chaperone gp96 is essential for infection with vesicular stomatitis virus |
| |
| Authors: | Stuart Bloor Jonathan Maelfait Rebekka Krumbach Rudi Beyaert Felix Randow |
| |
| Institution: | aDivision of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge CB0 2QH, United Kingdom;;bUnit of Molecular Signal Transduction in Inflammation, Department for Molecular Biomedical Research, Flanders Institute for Biotechnology, B-9052 Ghent, Belgium; and;cDepartment of Molecular Biology, Ghent University, B-9052 Ghent, Belgium |
| |
| Abstract: | The envelope glycoprotein of vesicular stomatitis virus (VSV-G) enables viral entry into hosts as distant as insects and vertebrates. Because of its ability to support infection of most, if not all, human cell types VSV-G is used in viral vectors for gene therapy. However, neither the receptor nor any specific host factor for VSV-G has been identified. Here we demonstrate that infection with VSV and innate immunity via Toll-like receptors (TLRs) require a shared component, the endoplasmic reticulum chaperone gp96. Cells without gp96 or with catalytically inactive gp96 do not bind VSV-G. The ubiquitous expression of gp96 is therefore essential for the remarkably broad tropism of VSV-G. Cells deficient in gp96 also lack functional TLRs, which suggests that pathogen-driven pressure for TLR-mediated immunity maintains the broad host range of VSV-G by positively selecting for the ubiquitous expression of gp96. |
| |
| Keywords: | host factor innate immunity toll-like receptor grp94 |
|
|
