title: Comprehensive analysis of herpes simplex virus 1 (HSV-1) entry mediated by zebrafish 3-O-Sulfotransferase isoforms: implications for the development of a zebrafish model of HSV-1 infection.
abstract: Binding of herpes simplex virus 1 (HSV-1) envelope glycoprotein D (gD) to the receptor 3-O-sulfated heparan sulfate (3-OS HS) mediates viral entry. 3-O-Sulfation of HS is catalyzed by the 3-O-sulfotransferase (3-OST) enzyme. Multiple isoforms of 3-OST are differentially expressed in tissues of zebrafish (ZF) embryos. Here, we performed a comprehensive analysis of the role of ZF 3-OST isoforms (3-OST-1, 3-OST-5, 3-OST-6, and 3-OST-7) in HSV-1 entry. We found that a group of 3-OST gene family isoforms (3-OST-2, -3, -4, and -6) with conserved catalytic and substrate-binding residues of the enzyme mediates HSV-1 entry and spread, while the other group (3-OST-1, -5, and -7) lacks these properties. These results demonstrate that HSV-1 entry can be recapitulated by certain ZF 3-OST enzymes, a significant step toward the establishment of a ZF model of HSV-1 infection and tissue-specific tropism.
authors.affiliation: Department of Ophthalmology and Visual Sciences and Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Abraam M
authors.initials: AM
authors.lastname: Yakoub
authors.affiliation: Department of Microbiology and Immunology, Midwestern University, Downers Grove, Illinois, USA.
authors.forename: Nistha
authors.initials: N
authors.lastname: Rawal
authors.affiliation: Department of Microbiology and Immunology, Midwestern University, Downers Grove, Illinois, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Maus
authors.affiliation: Department of Microbiology and Immunology, Midwestern University, Downers Grove, Illinois, USA.
authors.forename: John
authors.initials: J
authors.lastname: Baldwin
authors.affiliation: Department of Ophthalmology and Visual Sciences and Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
authors.affiliation: Department of Ophthalmology and Visual Sciences and Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois, USA Department of Microbiology and Immunology, Midwestern University, Downers Grove, Illinois, USA vtiwar@midwestern.edu.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Tiwari
mesh_terms: D000818:Animals; D006497:Heparan Sulfate / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism*; D053586:Virus Internalization; D015027:Zebrafish / Q000821:virology*
chemical_list: D006497:Heparan Sulfate; D020033:Protein Isoforms; D011991:Receptors, Virus; D015238:Sulfotransferases