title: Characterization of the receptor-binding domain of Ebola glycoprotein in viral entry.
abstract: Ebola virus infection causes severe hemorrhagic fever in human and non-human primates with high mortality. Viral entry/infection is initiated by binding of glycoprotein GP protein on Ebola virion to host cells, followed by fusion of virus-cell membrane also mediated by GP. Using an human immunodeficiency virus (HIV)-based pseudotyping system, the roles of 41 Ebola GP1 residues in the receptor-binding domain in viral entry were studied by alanine scanning substitutions. We identified that four residues appear to be involved in protein folding/structure and four residues are important for viral entry. An improved entry interference assay was developed and used to study the role of these residues that are important for viral entry. It was found that R64 and K95 are involved in receptor binding. In contrast, some residues such as I170 are important for viral entry, but do not play a major role in receptor binding as indicated by entry interference assay and/or protein binding data, suggesting that these residues are involved in post-binding steps of viral entry. Furthermore, our results also suggested that Ebola and Marburg viruses share a common cellular molecule for entry.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, USA.
authors.forename: Jizhen
authors.initials: J
authors.lastname: Wang
authors.forename: Balaji
authors.initials: B
authors.lastname: Manicassamy
authors.forename: Michael
authors.initials: M
authors.lastname: Caffrey
authors.forename: Lijun
authors.initials: L
authors.lastname: Rong
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002460:Cell Line; D029043:Ebolavirus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019142:Hemorrhagic Fever, Ebola / Q000378:metabolism / Q000821:virology*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus