A role for 3-O-sulfated heparan sulfate in cell fusion induced by herpes simplex virus type 1.
Membrane fusion induced by herpes simplex virus (HSV) is required for both entry and cell-to-cell spread. It is mediated by the viral glycoprotein gB, gD, gH-gL and gD receptors. Although 3-O-sulfated heparan sulfate (3-OS HS) is a receptor for HSV-1 entry, the requirement for heparan sulfate in the fusion process has been ruled out. Here, it is demonstrated that cells expressing 3-OS HS, generated by D-glucosaminyl 3-O-sulfotransferase isoforms-3 and/or -5 (3-OST-3 and 3-OST-5), fused with cells expressing the four glycoproteins. The cell fusion observed exhibited similar requirements but was independent of protein receptors, HVEM or nectin-1. Additionally, removal of 3-OS HS from the cell surface by heparinase-I treatment and, in separate experiments, the presence of soluble 3-OST-3- and 3-OST-5-modified HS, significantly inhibited fusion. Taken together, these results indicate that 3-OS HS can play a crucial role in virus entry and cell fusion.
Tiwari
Vaibhav
V
Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Clement
Christian
C
Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Duncan
Michael B
MB
Divison of Medicinal Chemistry and Natural Products, University of North Carolina, Chapel Hill, NC 27599, USA.
Chen
Jinghua
J
Divison of Medicinal Chemistry and Natural Products, University of North Carolina, Chapel Hill, NC 27599, USA.
Liu
Jian
J
Divison of Medicinal Chemistry and Natural Products, University of North Carolina, Chapel Hill, NC 27599, USA.
Shukla
Deepak
D
Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.|Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006497:Heparan Sulfate / Q000737:chemistry / Q000502:physiology*; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology*; D011991:Receptors, Virus / Q000737:chemistry / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D006497:Heparan Sulfate; D007527:Isoenzymes; D011991:Receptors, Virus; D011994:Recombinant Proteins; D015238:Sulfotransferases; C049545:simplexvirus receptor; C021350:heparitin sulfotransferase