EMD-21509
Human mAbs broadly protect against infection of arthritiogenic alphaviruses by recognizing conserved elements of the MXR8 receptor binding domain
EMD-21509
Single-particle5.3 Å
Deposition: 04/03/2020
Map released: 26/08/2020
Last modified: 06/03/2024
Sample Organism:
Homo sapiens,
Mayaro virus (strain Brazil),
Mayaro virus
Sample: Mayaro virus-Fab CHK-265 complex
Fitted models: 6w1c (Avg. Q-score: 0.35)
Deposition Authors: Miller AS, Kuhn RJ
Sample: Mayaro virus-Fab CHK-265 complex
Fitted models: 6w1c (Avg. Q-score: 0.35)
Deposition Authors: Miller AS, Kuhn RJ
Human mAbs Broadly Protect against Arthritogenic Alphaviruses by Recognizing Conserved Elements of the Mxra8 Receptor-Binding Site.
Powell LA,
Miller A,
Fox JM,
Kose N,
Klose T,
Kim AS ,
Bombardi R,
Tennekoon RN,
Dharshan de Silva A,
Carnahan RH,
Diamond MS,
Rossmann MG,
Kuhn RJ,
Crowe Jr JE
(2020) Cell Host Microbe , 28 , 699 - 711.e7
(2020) Cell Host Microbe , 28 , 699 - 711.e7
Abstract:
Mosquito inoculation of humans with arthritogenic alphaviruses results in a febrile syndrome characterized by debilitating musculoskeletal pain and arthritis. Despite an expanding global disease burden, no approved therapies or licensed vaccines exist. Here, we describe human monoclonal antibodies (mAbs) that bind to and neutralize multiple distantly related alphaviruses. These mAbs compete for an antigenic site and prevent attachment to the recently discovered Mxra8 alphavirus receptor. Three cryoelectron microscopy structures of Fab in complex with Ross River (RRV), Mayaro, or chikungunya viruses reveal a conserved footprint of the broadly neutralizing mAb RRV-12 in a region of the E2 glycoprotein B domain. This mAb neutralizes virus in vitro by preventing virus entry and spread and is protective in vivo in mouse models. Thus, the RRV-12 mAb and its defined epitope have potential as a therapeutic agent or target of vaccine design against multiple emerging arthritogenic alphavirus infections.
Mosquito inoculation of humans with arthritogenic alphaviruses results in a febrile syndrome characterized by debilitating musculoskeletal pain and arthritis. Despite an expanding global disease burden, no approved therapies or licensed vaccines exist. Here, we describe human monoclonal antibodies (mAbs) that bind to and neutralize multiple distantly related alphaviruses. These mAbs compete for an antigenic site and prevent attachment to the recently discovered Mxra8 alphavirus receptor. Three cryoelectron microscopy structures of Fab in complex with Ross River (RRV), Mayaro, or chikungunya viruses reveal a conserved footprint of the broadly neutralizing mAb RRV-12 in a region of the E2 glycoprotein B domain. This mAb neutralizes virus in vitro by preventing virus entry and spread and is protective in vivo in mouse models. Thus, the RRV-12 mAb and its defined epitope have potential as a therapeutic agent or target of vaccine design against multiple emerging arthritogenic alphavirus infections.