title: Mannose-binding lectin binds to Ebola and Marburg envelope glycoproteins, resulting in blocking of virus interaction with DC-SIGN and complement-mediated virus neutralization.
abstract: Mannose-binding lectin (MBL), a serum lectin that mediates innate immune functions including activation of the lectin complement pathway, binds to carbohydrates expressed on some viral glycoproteins. In this study, the ability of MBL to bind to virus particles pseudotyped with Ebola and Marburg envelope glycoproteins was evaluated. Virus particles bearing either Ebola (Zaire strain) or Marburg (Musoke strain) envelope glycoproteins bound at significantly higher levels to immobilized MBL compared with virus particles pseudotyped with vesicular stomatitis virus glycoprotein or with no virus glycoprotein. As observed in previous studies, Ebola-pseudotyped virus bound to cells expressing the lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin). However, pre-incubation of virus with MBL blocked DC-SIGN-mediated binding to cells, suggesting that the two lectins bind at the same or overlapping sites on the Ebola glycoprotein. Neutralization experiments showed that virus pseudotyped with Ebola or Marburg (Musoke) glycoprotein was neutralized by complement, while the Marburg (Ravn strain) glycoprotein-pseudotyped virus was less sensitive to neutralization. Neutralization was partially mediated through the lectin complement pathway, since a complement source deficient in MBL was significantly less effective at neutralizing viruses pseudotyped with filovirus glycoproteins and addition of purified MBL to the MBL-deficient complement increased neutralization. These experiments demonstrated that MBL binds to filovirus envelope glycoproteins resulting in important biological effects and suggest that MBL can interact with filoviruses during infection in humans.
authors.affiliation: Rush St Luke's Medical Center, Department of Immunology and Microbiology, 1653 W. Congress Parkway, Chicago, IL 60612, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Ji
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Division of Virology, 1425 Porter Street, Frederick, MD 21702-5011, USA.
authors.forename: Gene G
authors.initials: GG
authors.lastname: Olinger
authors.affiliation: Rush St Luke's Medical Center, Department of Immunology and Microbiology, 1653 W. Congress Parkway, Chicago, IL 60612, USA.
authors.forename: Sheena
authors.initials: S
authors.lastname: Aris
authors.affiliation: Rush St Luke's Medical Center, Department of Immunology and Microbiology, 1653 W. Congress Parkway, Chicago, IL 60612, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Rush St Luke's Medical Center, Department of Immunology and Microbiology, 1653 W. Congress Parkway, Chicago, IL 60612, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Gewurz
authors.affiliation: Rush St Luke's Medical Center, Department of Immunology and Microbiology, 1653 W. Congress Parkway, Chicago, IL 60612, USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Spear
mesh_terms: D001667:Binding, Competitive; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D003165:Complement System Proteins / Q000378:metabolism; D029043:Ebolavirus / Q000378:metabolism* / Q000472:pathogenicity; D015686:Gene Products, env / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D037601:Mannose-Binding Lectin / Q000378:metabolism*; D029024:Marburgvirus / Q000378:metabolism* / Q000472:pathogenicity; D009500:Neutralization Tests; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D003165:Complement System Proteins; D015686:Gene Products, env; D037181:Lectins, C-Type; D037601:Mannose-Binding Lectin; D011956:Receptors, Cell Surface; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C113189:envelope glycoprotein, Ebola virus