title: Fine mapping and interaction analysis of a linear rabies virus neutralizing epitope.
abstract: A novel human antibody AR16, targeting the G5 linear epitope of rabies virus glycoprotein (RVG) was shown to have promising antivirus potency. Using AR16, the minimal binding region within G5 was identified as HDFR (residues 261-264), with key residues HDF (residues 261-263) identified by alanine replacement scanning. The key HDF was highly conserved within phylogroup I Lyssaviruses but not those in phylogroup II. Using computer-aided docking and interaction models, not only the key residues (Asp30, Asp31, Tyr32, Trp53, Asn54, Glu99, Ile101, and Trp166) of AR16 that participated in the interaction with G5 were identified, the van der Waals forces that mediated the epitope-antibody interaction were also revealed. Seven out of eight presumed key residues (Asp30, Asp31, Tyr32, Trp53, Asn54, Glu99, and Ile101) were located at the variable regions of AR16 heavy chains. A novel mAb cocktail containing AR16 and CR57, has the potential to recognize non-overlapping, non-competing epitopes, and neutralize a broad range of rabies virus.
authors.affiliation: State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, No. 20 Dongdajie, Fengtai District, Beijing 100071, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Cai
authors.forename: Jian-nan
authors.initials: JN
authors.lastname: Feng
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Hou
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Tu
authors.forename: Le
authors.initials: L
authors.lastname: Xiao
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D019943:Amino Acid Substitution; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D001665:Binding Sites; D017124:Conserved Sequence; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011820:Rabies virus / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes