Chondroitin 4-O-sulfotransferase-1 regulates E disaccharide expression of chondroitin sulfate required for herpes simplex virus infectivity.
We have demonstrated a defect in expression of chondroitin 4-O-sulfotransferase-1 (C4ST-1) in murine sog9 cells, which are poorly sensitive to infection by herpes simplex virus type 1 (HSV-1). Sog9 cells were previously isolated as CS-deficient cells from gro2C cells, which were partially resistant to HSV-1 infection and defective in the expression of heparan sulfate (HS) because of a splice site mutation in the EXT1 gene encoding the HS-synthesizing enzyme. Here we detected a small amount of CS chains in sog9 cells with a drastic decrease in 4-O-sulfation compared with the parental gro2C cells. RT-PCR revealed that sog9 cells had a defect in the expression of C4ST-1 in addition to EXT1. Gel filtration analysis showed that the decrease in the amount of CS in sog9 cells was the result of a reduction in the length of CS chains. Transfer of C4ST-1 cDNA into sog9 cells (sog9-C4ST-1) restored 4-O-sulfation and amount of CS, verifying that sog9 cells had a specific defect in C4ST-1. Furthermore, the expression of C4ST-1 rendered sog9 cells significantly more susceptible to HSV-1 infection, suggesting that CS modified by C4ST-1 is sufficient for the binding and infectivity of HSV-1. Analysis of CS chains of gro2C and sog9-C4ST-1 cells revealed a considerable proportion of the E disaccharide unit, consistent with our recent finding that this unit is an essential component of the HSV receptor. These results suggest that C4ST-1 regulates the expression of the E disaccharide unit and the length of CS chains, the features that facilitate infection of cells by HSV-1.
Uyama
Toru
T
Department of Biochemistry, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.
Ishida
Miho
M
Izumikawa
Tomomi
T
Trybala
Edward
E
Tufaro
Frank
F
Bergström
Tomas
T
Sugahara
Kazuyuki
K
Kitagawa
Hiroshi
H
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000378:metabolism*; D017931:DNA Primers; D004187:Disaccharides / Q000494:pharmacology*; D007150:Immunohistochemistry; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus / Q000472:pathogenicity*; D015238:Sulfotransferases / Q000378:metabolism*; D014774:Virulence
D017931:DNA Primers; D004187:Disaccharides; D002809:Chondroitin Sulfates; D015238:Sulfotransferases; C019893:chondroitin 4-sulfotransferase