Preexisting and de novo humoral immunity to SARS-CoV-2 in humansZoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, we detected preexisting humoral immunity. SARS-CoV-2 spike glycoprotein (S)-reactive antibodies were detectable using a flow cytometry-based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. They were predominantly of the immunoglobulin G (IgG) class and targeted the S2 subunit. By contrast, SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S-reactive IgG antibodies targeting both the S1 and S2 subunits, and concomitant IgM and IgA antibodies, lasting throughout the observation period. SARS-CoV-2-uninfected donor sera exhibited specific neutralizing activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes. Distinguishing preexisting and de novo immunity will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.
The effect of the D614G substitution on the structure of the spike glycoprotein of SARS-CoV-2D.J. Benton, Antoni G. Wrobel, Chloë Roustan et al.|Proceedings of the National Academy of Sciences|2021 Significance The spike proteins of most current severe acute respiratory syndrome coronavirus 2 isolates contain a D614G substitution, by comparison with the spike protein of initial isolates. In this study we present high-resolution, single-particle cryo-electron microscopy structures of the G614 spike variant showing that it adopts a predominantly open conformation, unlike the D614 spike that is mostly closed. We conclude that the D614G substitution promotes “opening” of the spike, priming it for binding to the receptor ACE2 and possibly for its subsequent role in membrane fusion. The observed open conformation of the G614 spike may be the reason for the current virus’ reported increased infectivity and its current predominance.
Influenza hemagglutinin membrane anchorD.J. Benton, Andrea Nans, Lesley J. Calder et al.|Proceedings of the National Academy of Sciences|2018 Viruses with membranes fuse them with cellular membranes, to transfer their genomes into cells at the beginning of infection. For Influenza virus, the membrane glycoprotein involved in fusion is the hemagglutinin (HA), the 3D structure of which is known from X-ray crystallographic studies. The soluble ectodomain fragments used in these studies lacked the "membrane anchor" portion of the molecule. Since this region has a role in membrane fusion, we have determined its structure by analyzing the intact, full-length molecule in a detergent micelle, using cryo-EM. We have also compared the structures of full-length HA-detergent micelles with full-length HA-Fab complex detergent micelles, to describe an infectivity-neutralizing monoclonal Fab that binds near the ectodomain membrane anchor junction. We determine a high-resolution HA structure which compares favorably in detail with the structure of the ectodomain seen by X-ray crystallography; we detect, clearly, all five carbohydrate side chains of HA; and we find that the ectodomain is joined to the membrane anchor by flexible, eight-residue-long, linkers. The linkers extend into the detergent micelle to join a central triple-helical structure that is a major component of the membrane anchor.