8TNN

Crystal structure of Epstein-Barr virus gH/gL/gp42 in complex with gp42 antibody A10

Summary for 8TNN

• Entry DOI: 10.2210/pdb8tnn/pdb
• Descriptor: Envelope glycoprotein H, Envelope glycoprotein L, Glycoprotein 42, ... (7 entities in total)
• Functional Keywords: viral protein, antibody, immune system
• Biological source: Human herpesvirus 4 strain B95-8 (Epstein-Barr virus); More
• Total number of polymer chains: 10
• Total formula weight: 312859.45

Authors

Bu, W.,Kumar, A.,Board, N.,Kim, J.,Dowdell, K.,Zhang, S.,Lei, Y.,Hostal, A.,Krogmann, T.,Wang, Y.,Pittaluga, S.,Marcotrigiano, J.,Cohen, J.I. (deposition date: 2023-08-02, release date: 2024-03-27, Last modification date: 2024-10-09)

Primary citation

Bu, W.,Kumar, A.,Board, N.L.,Kim, J.,Dowdell, K.,Zhang, S.,Lei, Y.,Hostal, A.,Krogmann, T.,Wang, Y.,Pittaluga, S.,Marcotrigiano, J.,Cohen, J.I.
Epstein-Barr virus gp42 antibodies reveal sites of vulnerability for receptor binding and fusion to B cells.
Immunity, 57:559-573.e6, 2024

PubMed Abstract: Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with B cell lymphomas. EBV glycoprotein 42 (gp42) binds HLA class II and activates membrane fusion with B cells. We isolated gp42-specific monoclonal antibodies (mAbs), A10 and 4C12, which use distinct mechanisms to neutralize virus infection. mAb A10 was more potent than the only known neutralizing gp42 mAb, F-2-1, in neutralizing EBV infection and blocking binding to HLA class II. mAb 4C12 was similar to mAb A10 in inhibiting glycoprotein-mediated B cell fusion but did not block receptor binding, and it was less effective in neutralizing infection. Crystallographic structures of gH/gL/gp42/A10 and gp42/4C12 complexes revealed two distinct sites of vulnerability on gp42 for receptor binding and B cell fusion. Passive transfer of mAb A10 into humanized mice conferred nearly 100% protection from viremia and EBV lymphomas after EBV challenge. These findings identify vulnerable sites on EBV that may facilitate therapeutics and vaccines.

PubMed: 38479361
DOI: 10.1016/j.immuni.2024.02.008

Experimental method

X-RAY DIFFRACTION (3.36 Å)