8DBZ

CryoEM structure of Hantavirus ANDV Gn(H) protein complex with 2Fabs ANDV-5 and ANDV-34

Summary for 8DBZ

• Entry DOI: 10.2210/pdb8dbz/pdb
• EMDB information: 26735 26736 27318
• Descriptor: Glycoprotein N, Fv (H) ANDV-34, Fv (L) ANDV-34, ... (7 entities in total)
• Functional Keywords: fab, viral protein-immune system complex, viral protein/immune system
• Biological source: Andes orthohantavirus; More
• Total number of polymer chains: 9
• Total formula weight: 135357.83

Authors

Binshtein, E.,Crowe, J.E. (deposition date: 2022-06-15, release date: 2023-04-05, Last modification date: 2024-10-09)

Primary citation

Engdahl, T.B.,Binshtein, E.,Brocato, R.L.,Kuzmina, N.A.,Principe, L.M.,Kwilas, S.A.,Kim, R.K.,Chapman, N.S.,Porter, M.S.,Guardado-Calvo, P.,Rey, F.A.,Handal, L.S.,Diaz, S.M.,Zagol-Ikapitte, I.A.,Tran, M.H.,McDonald, W.H.,Meiler, J.,Reidy, J.X.,Trivette, A.,Bukreyev, A.,Hooper, J.W.,Crowe Jr., J.E.
Antigenic mapping and functional characterization of human new world hantavirus neutralizing antibodies.
Elife, 12:-, 2023

PubMed Abstract: Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans by aerosolized excreta or, in rare cases, person-to-person contact. While infections in humans are relatively rare, mortality rates range from 1 to 40% depending on the hantavirus species. There are currently no FDA-approved vaccines or therapeutics for hantaviruses, and the only treatment for infection is supportive care for respiratory or kidney failure. Additionally, the human humoral immune response to hantavirus infection is incompletely understood, especially the location of major antigenic sites on the viral glycoproteins and conserved neutralizing epitopes. Here, we report antigenic mapping and functional characterization for four neutralizing hantavirus antibodies. The broadly neutralizing antibody SNV-53 targets an interface between Gn/Gc, neutralizes through fusion inhibition and cross-protects against the Old World hantavirus species Hantaan virus when administered pre- or post-exposure. Another broad antibody, SNV-24, also neutralizes through fusion inhibition but targets domain I of Gc and demonstrates weak neutralizing activity to authentic hantaviruses. ANDV-specific, neutralizing antibodies (ANDV-5 and ANDV-34) neutralize through attachment blocking and protect against hantavirus cardiopulmonary syndrome (HCPS) in animals but target two different antigenic faces on the head domain of Gn. Determining the antigenic sites for neutralizing antibodies will contribute to further therapeutic development for hantavirus-related diseases and inform the design of new broadly protective hantavirus vaccines.

PubMed: 36971354
DOI: 10.7554/eLife.81743

Experimental method

ELECTRON MICROSCOPY (4.1 Å)