7O9S

Hantaan virus Gn in complex with Fab nnHTN-Gn2

7O9S の概要

• エントリーDOI: 10.2210/pdb7o9s/pdb
• 分子名称: Fab nnHTN-Gn2 Heavy chain, Fab nnHTN-Gn2 Light chain, Envelope polyprotein, ... (5 entities in total)
• 機能のキーワード: hantaan virus glycoprotein, gn glycoprotein, gn in complex with fab, neutralizing antibody, viral glycoprotein in complex with antibody, viral protein
• 由来する生物種: Oryctolagus cuniculus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 87973.70

構造登録者

Rissanen, I.,Bowden, T.A.,Huiskonen, J.T.,Stass, R. (登録日: 2021-04-16, 公開日: 2021-06-23, 最終更新日: 2024-11-13)

主引用文献

Rissanen, I.,Krumm, S.A.,Stass, R.,Whitaker, A.,Voss, J.E.,Bruce, E.A.,Rothenberger, S.,Kunz, S.,Burton, D.R.,Huiskonen, J.T.,Botten, J.W.,Bowden, T.A.,Doores, K.J.
Structural Basis for a Neutralizing Antibody Response Elicited by a Recombinant Hantaan Virus Gn Immunogen.
Mbio, 12:e0253120-e0253120, 2021

PubMed Abstract: Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two glycoproteins, Gn and Gc, which are responsible for negotiating host cell entry and constitute key therapeutic targets. Here, we demonstrate that recombinantly derived Gn from Hantaan virus (HTNV) elicits a neutralizing antibody response (serum dilution that inhibits 50% infection [ID], 1:200 to 1:850) in an animal model. Using antigen-specific B cell sorting, we isolated monoclonal antibodies (mAbs) exhibiting neutralizing and non-neutralizing activity, termed mAb HTN-Gn1 and mAb nnHTN-Gn2, respectively. Crystallographic analysis reveals that these mAbs target spatially distinct epitopes at disparate sites of the N-terminal region of the HTNV Gn ectodomain. Epitope mapping onto a model of the higher order (Gn-Gc) spike supports the immune accessibility of the mAb HTN-Gn1 epitope, a hypothesis confirmed by electron cryo-tomography of the antibody with virus-like particles. These data define natively exposed regions of the hantaviral Gn that can be targeted in immunogen design. The spillover of pathogenic hantaviruses from rodent reservoirs into the human population poses a continued threat to human health. Here, we show that a recombinant form of the Hantaan virus (HTNV) surface-displayed glycoprotein, Gn, elicits a neutralizing antibody response in rabbits. We isolated a neutralizing (HTN-Gn1) and a non-neutralizing (nnHTN-Gn2) monoclonal antibody and provide the first molecular-level insights into how the Gn glycoprotein may be targeted by the antibody-mediated immune response. These findings may guide rational vaccine design approaches focused on targeting the hantavirus glycoprotein envelope.

PubMed: 34225492
DOI: 10.1128/mBio.02531-20

実験手法

X-RAY DIFFRACTION (2.7 Å)