Allen ER
Krumm SA
Raghwani J
Halldorsson S
Elliott A
Graham VA
Koudriakova E
Harlos K
Wright D
Warimwe GM
Brennan B
Huiskonen JT
Dowall SD
Elliott RM
Pybus OG
Burton DR
Hewson R
Doores KJ
Bowden TA
Cell Rep. 2018;253750-3758 e4
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.
