Structural studies on antibody recognition and neutralization of viruses

Abstract

The purpose of this brief review is to highlight how structural information can elucidate antibody recognition and neutralization of viruses. Studies on human rhinovirus demonstrated that antibodies need not induce conformational changes for neutralization and that viruses do not conceal receptor-binding regions from immune recognition. Ross River and Sindbis virus complexes were an early example of using antibodies to demark receptor-binding regions. The structure of an antibody bound to mouse norovirus is an example of antibodies binding to sharp protrusions on flexible receptor-binding domains. Finally, the structure of cucumber mosaic virus bound to a loop involved in aphid transmission demonstrated the importance of the context of antigen presentation and what happens when an antibody binds near an icosahedral symmetry axis.

Figure 1

Composite picture of the structures of several antibody/virus complexes. In all cases, the antibodies are represented in various colors while the capsid surface itself is shown in grey.

Figure 2

Details of two very different antibody/virus contacts. The ribbon diagram on the left represents the crystal structure of the Fab17/HRV14 complex. In this case, the hypervariable loops on the Fab cover the NIm-IA site and the heavy chain makes extensive contacts with the north and south walls of the receptorbinding region. On the right is hybrid structure of MNV-1 using the cryo-TEM structure of the MNV/Fab complex and the atomic structure of the MNV P domain. In this case, the epitope lies on a sharp protrusion to which the antibody makes contact.