Convergent Structures Illuminate Features for Germline Antibody Binding and Pan-Lassa Virus Neutralization.

ABSTRACT: Lassa virus (LASV) causes hemorrhagic fever and is endemic in West Africa. Protective antibody responses primarily target the LASV surface glycoprotein (GPC), and GPC-B competition group antibodies often show potent neutralizing activity in humans. However, which features confer potent and broadly neutralizing antibody responses is unclear. Here, we compared three crystal structures of LASV GPC complexed with GPC-B antibodies of varying neutralization potency. Each GPC-B antibody recognized an overlapping epitope involved in binding of two adjacent GPC monomers and preserved the prefusion trimeric conformation. Differences among GPC-antibody interactions highlighted specific residues that enhance neutralization. Using structure-guided amino acid substitutions, we increased the neutralizati

SUBMITTER: Hastie KM 

PROVIDER: S-EPMC6814208 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature