- PDB-7o9s: Hantaan virus Gn in complex with Fab nnHTN-Gn2 -
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IDまたはキーワード:
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基本情報
登録情報
データベース: PDB / ID: 7o9s
タイトル
Hantaan virus Gn in complex with Fab nnHTN-Gn2
要素
Envelope polyprotein
Fab nnHTN-Gn2 Heavy chain
Fab nnHTN-Gn2 Light chain
キーワード
VIRAL PROTEIN / Hantaan virus glycoprotein / Gn glycoprotein / Gn in complex with Fab / neutralizing antibody / viral glycoprotein in complex with antibody
機能・相同性
機能・相同性情報
symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / host cell surface / host cell endoplasmic reticulum membrane / symbiont-mediated suppression of host innate immune response / symbiont entry into host cell / fusion of virus membrane with host endosome membrane / virion attachment to host cell / virion membrane ...symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / host cell surface / host cell endoplasmic reticulum membrane / symbiont-mediated suppression of host innate immune response / symbiont entry into host cell / fusion of virus membrane with host endosome membrane / virion attachment to host cell / virion membrane / signal transduction / zinc ion binding / membrane 類似検索 - 分子機能
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R41AI132047
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R41AI132047-01S1
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R43AI142911
米国
Wellcome Trust
203141/Z/16/Z
英国
Wellcome Trust
093305/Z/10/Z
英国
引用
ジャーナル: mBio / 年: 2021 タイトル: Structural Basis for a Neutralizing Antibody Response Elicited by a Recombinant Hantaan Virus Gn Immunogen. 著者: Ilona Rissanen / Stefanie A Krumm / Robert Stass / Annalis Whitaker / James E Voss / Emily A Bruce / Sylvia Rothenberger / Stefan Kunz / Dennis R Burton / Juha T Huiskonen / Jason W Botten / ...著者: Ilona Rissanen / Stefanie A Krumm / Robert Stass / Annalis Whitaker / James E Voss / Emily A Bruce / Sylvia Rothenberger / Stefan Kunz / Dennis R Burton / Juha T Huiskonen / Jason W Botten / Thomas A Bowden / Katie J Doores / 要旨: 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 ...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.