Mediation of virion penetration into vascular cells by association of basic fibroblast growth factor with herpes simplex virus type 1.
Herpes simplex virus type-1 (HSV-1) is a ubiquitous pathogen that is associated with considerable morbidity in the general population. Although it is known that the virion uses a basic fibroblast growth factor (FGF) receptor to penetrate vascular cells, it is not known how the viral particle recognizes and binds to this cell surface protein. Here we report that an immunoreactive basic FGF-like protein is associated with the viral particle and that this association appears responsible for viral uptake. Accordingly, HSV-1 infection of Swiss 3T3 cells stimulates the tyrosine phosphorylation of the specific substrate that characterizes the initial cellular response to basic FGF. Antibodies to basic FGF prevent this phosphorylation and inhibit HSV-1 uptake. Because no basic FGF sequence is found in the HSV-1 genome, a model for the infection for some target cells is presented whereby the viral particle uses host cell-derived basic FGF to ensure subsequent infectivity of newly replicated virus.
Baird
A
A
Department of Molecular and Cellular Growth Biology, Whittler Institute for Diabetes and Endocrinology, La Jolla, California 92037.
Florkiewicz
R Z
RZ
Maher
P A
PA
Kaner
R J
RJ
Hajjar
D P
DP
D000818:Animals; D002460:Cell Line; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D007700:Kinetics; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins / Q000378:metabolism; D018139:Simplexvirus / Q000378:metabolism / Q000502:physiology*; D014771:Virion / Q000378:metabolism / Q000502:physiology*
D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2