Antibody barriers to going viral

Abstract

Antibody neutralization of a virus in vitro is often associated with protection against viral exposure in vivo, but the mechanisms operational in vivo are often unclear. By investigating a large number of antibodies, Earnest et al. (https://doi.org/10.1084/jem.20190736) show the importance of antibody effector function in neutralizing antibody protection against an emerging alphavirus in a mouse model.

Insights from Dennis R. Burton.

Ab linking infected cell and effector cell: interactions in a tight space. Earnest et al. (2019) show that nAb protection against MAYV requires Ab interaction with an effector function, most likely an Fc receptor–bearing cell. The type of interaction probably involved is modeled here using available structures and known interaction sites. The alphavirus Chikungunya E1 (pale orange) and E2 (orange) spike proteins (PDB 6NK5), full length human IgG (IgG b12, PDB 1HZH, bright and dark blue), and Fc-bound human FcγRIIa (PDB 3RY6, red) structures are modeled together to reveal the tight space in which the three-way interaction occurs. To avoid structural clashes, the immunoglobulin Fab arms are bent away from the bound Fcγ receptor, and the Fc portion is lain flat on the surface of the Fc-bearing cell (pink) in order to allow for insertion of the C-terminal end of the FcγR into the cell membrane. The side view shows the three molecules involved, but the Fc is not well seen; this is clearer in the top view. Modeling and 3D rendering by Christina Corbaci and Lars Hangartner.