title: An important role for syndecan-1 in herpes simplex virus type-1 induced cell-to-cell fusion and virus spread.
abstract: Herpes simplex virus type-1 (HSV-1) is a common human pathogen that relies heavily on cell-to-cell spread for establishing a lifelong latent infection. Molecular aspects of HSV-1 entry into host cells have been well studied; however, the molecular details of the spread of the virus from cell-to-cell remain poorly understood. In the past, the role of heparan sulfate proteoglycans (HSPG) during HSV-1 infection has focused solely on the role of HS chains as an attachment receptor for the virus, while the core protein has been assumed to perform a passive role of only carrying the HS chains. Likewise, very little is known about the involvement of any specific HSPGs in HSV-1 lifecycle. Here we demonstrate that a HSPG, syndecan-1, plays an important role in HSV-1 induced membrane fusion and cell-to-cell spread. Interestingly, the functions of syndecan-1 in fusion and spread are independent of the presence of HS on the core protein. Using a mutant CHO-K1 cell line that lacks all glycosaminoglycans (GAGs) on its surface (CHO-745) we demonstrate that the core protein of syndecan-1 possesses the ability to modulate membrane fusion and viral spread. Altogether, we identify a new role for syndecan-1 in HSV-1 pathogenesis and demonstrate HS-independent functions of its core protein in viral spread.
authors.affiliation: Department of Ophthalmology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, United States of America.
authors.forename: Ghadah A
authors.initials: GA
authors.lastname: Karasneh
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ali
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
mesh_terms: D000818:Animals; D016466:CHO Cells; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D006224:Cricetinae; D003412:Cricetulus; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D015536:Down-Regulation; D019573:Epithelium, Corneal / Q000166:cytology / Q000821:virology; D055785:Gene Knockdown Techniques; D015726:Giant Cells / Q000166:cytology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009154:Mutation; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D053668:Syndecan-1 / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014760:Viral Fusion Proteins / Q000378:metabolism; D010948:Viral Plaque Assay; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D053668:Syndecan-1; D014760:Viral Fusion Proteins