title: Human herpesvirus 8 glycoprotein B binds the entry receptor DC-SIGN.
abstract: We have previously shown that human herpesvirus 8 (HHV-8) uses DC-SIGN as an entry receptor for dendritic cells, macrophages and B cells. The viral attachment protein for DC-SIGN is unknown. HHV-8 virions contain five conserved herpesvirus glycoproteins, a single unique glycoprotein, and two predicted glycoproteins. Previous studies have shown that DC-SIGN binds highly mannosylated glycoproteins. The HHV-8 glycoprotein B (gB) has been reported to be highly mannosylated, and therefore we hypothesized that gB will bind to DC-SIGN. In this report we confirm that gB has a high mannose carbohydrate structure and demonstrate for the first time that it binds DC-SIGN in a dose-dependent manner. We also identify key amino acids in the DC-SIGN carbohydrate recognition domain that are required for HHV-8 infection and compare these results with published binding regions for ICAM-2/3 and HIV-1 gp120. These results clarify some of the initial events in HHV-8 entry and can be used for the design of targeted preventive therapies.
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, Parran Hall, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Heather R
authors.initials: HR
authors.lastname: Hensler
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, Parran Hall, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Tomaszewski
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, Parran Hall, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rappocciolo
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, Parran Hall, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, Parran Hall, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA; University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh, PA 15213, USA. Electronic address: fjenkins@pitt.edu.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Jenkins
mesh_terms: D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006566:Herpesviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D019288:Herpesvirus 8, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C116207:glycoprotein B, human herpesvirus 8
keywords: DC-SIGN; Human herpesvirus 8