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A protective monoclonal antibody targets a site of vulnerability on the surface of Rift Valley Fever Virus
DOI:
10.1016/j.celrep.2018.12.001
Authors:
Elizabeth R.
Allen
(Wellcome Centre for Human Genetics, University of Oxford)
,
Stefanie A.
Krumm
(Kings College London)
,
Jayna
Raghwani
(University of Oxford)
,
Steinar
Halldorsson
(Wellcome Centre for Human Genetics, University of Oxford)
,
Angela
Elliott
(MRC-University of Glasgow Centre for Virus Research)
,
Victoria A.
Graham
(Public Health England)
,
Elina
Koudriakova
(MRC-University of Glasgow Centre for Virus Research)
,
Karl
Harlos
(Wellcome Centre for Human Genetics, University of Oxford)
,
Daniel
Wright
(The Jenner Institute, University of Oxford)
,
George M.
Warimwe
(University of Oxford; Kenya Medical Research Institute (KEMRI))
,
Benjamin
Brennan
(MRC-University of Glasgow Centre for Virus Research)
,
Juha T.
Huiskonen
(Wellcome Centre for Human Genetics, University of Oxford)
,
Stuart D.
Dowall
(Public Health England)
,
Richard M.
Elliott
(MRC-University of Glasgow Centre for Virus Research)
,
Oliver G.
Pybus
(University of Oxford)
,
Dennis R.
Burton
(The Scripps Research Institute; Ragon Institute of MGH, Harvard; MIT)
,
Roger
Hewson
(Public Health England)
,
Katie J.
Doores
(Kings College London)
,
Thomas A.
Bowden
(Wellcome Centre for Human Genetics, University of Oxford; The Scripps Research Institute)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Cell Reports
, VOL 25
, PAGES 3750 - 3758.e4
State:
Published (Approved)
Published:
December 2018
Diamond Proposal Number(s):
14744

Abstract: The Gn subcomponent of the Gn-Gc assembly that envelopes the human and animal pathogen, Rift Valley fever virus (RVFV), is a primary target of the neutralizing antibody response. To better understand the molecular basis for immune recognition, we raised a class of neutralizing monoclonal antibodies (nAbs) against RVFV Gn, which exhibited protective efficacy in a mouse infection model. Structural characterization revealed that these nAbs were directed to the membrane-distal domain of RVFV Gn and likely prevented virus entry into a host cell by blocking fusogenic rearrangements of the Gn-Gc lattice. Genome sequence analysis confirmed that this region of the RVFV Gn-Gc assembly was under selective pressure and constituted a site of vulnerability on the virion surface. These data provide a blueprint for the rational design of immunotherapeutics and vaccines capable of preventing RVFV infection and a model for understanding Ab-mediated neutralization of bunyaviruses more generally.
Journal Keywords: phlebovirus; Rift Valley fever virus; antibody; structure; bunyavirus; virus-host interactions; immune response; vaccine; antiviral; neutralization
Diamond Keywords: Viruses; Rift Valley Fever (RVF)
Subject Areas:
Biology and Bio-materials,
Medicine
Instruments:
I03-Macromolecular Crystallography
Added On:
08/01/2019 15:43
Documents:
1-s2.0-S2211124718319120-main.pdf
Discipline Tags:
Pathogens
Infectious Diseases
Disease in the Developing World
Health & Wellbeing
Structural biology
Drug Discovery
Life Sciences & Biotech
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)