Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1016/j.celrep.2018.12.001

Type

Journal article

Journal

Cell Rep

Publication Date

26/12/2018

Volume

25

Pages

3750 - 3758.e4

Keywords

Rift Valley fever virus, antibody, antiviral, bunyavirus, immune response, neutralization, phlebovirus, structure, vaccine, virus-host interactions, Amino Acid Sequence, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Chlorocebus aethiops, Female, Glycoproteins, HEK293 Cells, Humans, Immunization, Immunoglobulin G, Mice, Inbred BALB C, Models, Biological, Neutralization Tests, Protein Domains, Rabbits, Recombinant Proteins, Rift Valley fever virus, Vero Cells, Viral Envelope Proteins