Structural basis of synergistic neutralization of Crimean-Congo hemorrhagic fever virus by human antibodies

Abstract

A block to viral cell entry Crimean-Congo hemorrhagic fever virus is a tickborne virus that can cause severe disease and even death in humans. Disease occurrence is linked to the geographic range of the tick vector, and climate change may increase this range. Infection of host cells requires the fusion glycoprotein Gc, which is the main target of neutralizing antibodies. Mishra et al . build on previous work that identified a combination of two Gc-targeting antibodies that gave postexposure protection in an animal model. The authors determined the structure of the antigen-binding fragments of the two antibodies bound to a prefusion form of Gc and also the structure of Gc after the conformational change into the trimeric postfusion form. The structures show how the antibodies work together to block membrane fusion. —VV