Soluble 3-O-sulfated heparan sulfate can trigger herpes simplex virus type 1 entry into resistant Chinese hamster ovary (CHO-K1) cells.
Herpes simplex virus type 1 (HSV-1) interaction with glycoprotein D (gD) receptors facilitates virus entry into cells. Chinese hamster ovary (CHO-K1) cells lacking cellular receptors allow virus to attach, but not to enter, implying a role for receptors during the post-attachment (entry) phase of HSV-1 infection. Here, it is shown that the presence of soluble heparan sulfate (HS) modified by 3-O-sulfotransferase-3 (3-OST-3), but not by 3-OST-1, triggered HSV-1 entry into resistant CHO-K1 cells. It was further demonstrated that a CHO-K1 mutant deficient in glycosaminoglycan synthesis became susceptible to entry when spinoculated in the presence of 3-OST-3-modified soluble HS, indicating that the role of the gD receptor is to trigger entry rather than cell attachment. In separate experiments, 3-OST-3-modified soluble HS also triggered fusion of HSV-1 glycoprotein-expressing cells with CHO-K1 cells. Taken together, these results show that association of gD with cell surface-bound receptor is not essential for HSV-1 entry and spread.
Tiwari
Vaibhav
V
Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
O'Donnell
Christopher
C
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.
Copeland
Ronald J
RJ
Division of Medicinal Chemistry and Natural Products, University of North Carolina, Chapel Hill, NC 27599, USA.
Scarlett
Tanya
T
Division of Medicinal Chemistry and Natural Products, University of North Carolina, Chapel Hill, NC 27599, USA.
Liu
Jian
J
Division 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; D002459:Cell Fusion; D006224:Cricetinae; D003412:Cricetulus; D006025:Glycosaminoglycans / Q000172:deficiency; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology; D015238:Sulfotransferases / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects*
D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D011991:Receptors, Virus; D015238:Sulfotransferases; C021350:heparitin sulfotransferase