title: A role for 3-O-sulfated heparan sulfate in promoting human cytomegalovirus infection in human iris cells.
abstract: Human cytomegalovirus (HCMV) has emerged as a clinically opportunistic pathogen that targets multiple types of ocular cells and tissues, including the iris region of the uveal tract during anterior uveitis. In this report, we used primary cultures of human iris stroma (HIS) cells derived from human eye donors to investigate HCMV entry. The following lines of evidence suggested the role of 3-O-sulfated heparan sulfate (3-OS HS) during HCMV-mediated entry and cell-to-cell fusion in HIS cells. First, 3-O-sulfotransferase-3 (3-OST-3) expression in HIS cells promoted HCMV internalization, while pretreatment of HIS cells with heparinase enzyme or with anti-3-OS HS (G2) peptide significantly reduced the HCMV-mediated formation of plaques/foci. Second, coculture of the HCMV-infected HIS cells with CHO-K1 cells expressing 3-OS HS significantly enhanced cell fusion. Finally, a similar trend of enhanced fusion was observed with cells expressing HCMV glycoproteins (gB, gO, and gH-gL) cocultured with 3-OS HS cells. Taken together, these results highlight the role of 3-OS HS during HCMV plaque formation and cell-to-cell fusion and identify a novel target for future therapeutic interventions.
authors.affiliation: Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois, USA.
authors.forename: John
authors.initials: J
authors.lastname: Baldwin
authors.affiliation: Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Maus
authors.affiliation: Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Zanotti
authors.affiliation: Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Volin
authors.affiliation: Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Ritesh
authors.initials: R
authors.lastname: Tandon
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
authors.affiliation: Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois, USA Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, USA vtiwar@midwestern.edu.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Tiwari
mesh_terms: D000818:Animals; D002459:Cell Fusion; D002478:Cells, Cultured; D018920:Coculture Techniques; D006224:Cricetinae; D003587:Cytomegalovirus / Q000502:physiology*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D007498:Iris / Q000821:virology*; D011991:Receptors, Virus / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D006497:Heparan Sulfate; D011991:Receptors, Virus; D015238:Sulfotransferases; C021350:heparitin sulfotransferase