Endoplasmic reticulum chaperone gp96 is essential for infection with vesicular stomatitis virus.
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.
Bloor
Stuart
S
Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge CB0 2QH, United Kingdom.
Maelfait
Jonathan
J
Krumbach
Rebekka
R
Beyaert
Rudi
R
Randow
Felix
F
D002460:Cell Line; D018899:CpG Islands; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D018832:Molecular Chaperones / Q000737:chemistry; D016296:Mutagenesis; D012190:Retroviridae / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*
C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D051193:Toll-Like Receptors; D014168:Transferrin; D014759:Viral Envelope Proteins; C053387:endoplasmin