期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 28, 页码 7320-7325出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1803990115
关键词
Lassa virus; arenavirus; glycoprotein; structure; glycosylation
资金
- Medical Research Council (MRC) [MR/L009528/1]
- Bill & Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery Grant [OPP1115782]
- Scripps Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery Grant [1UM1AI100663]
- European Research Council [649053]
- Wellcome Trust (WT) [060208/Z/00/Z]
- WT [093305/Z/10/Z]
- WT
- Royal Society [107652/Z15/Z]
- German Research Foundation [SFB 1021 TP B05]
- [203141/Z/16/Z]
- European Research Council (ERC) [649053] Funding Source: European Research Council (ERC)
- MRC [MR/L009528/1, MR/N002091/1] Funding Source: UKRI
Lassa virus is an Old World arenavirus endemic to West Africa that causes severe hemorrhagic fever. Vaccine development has focused on the envelope glycoprotein complex (GPC) that extends from the virion envelope. The often inadequate antibody immune response elicited by both vaccine and natural infection has been, in part, attributed to the abundance of N-linked glycosylation on the GPC. Here, using a virus-like-particle system that presents Lassa virus GPC in a native-like context, we determine the composite population of each of the N-linked glycosylation sites presented on the trimeric GPC spike. Our analysis reveals the presence of underprocessed oligomannose-type glycans, which form punctuated clusters that obscure the proteinous surface of both the GP1 attachment and GP2 fusion glycoprotein subunits of the Lassa virus GPC. These oligomannose clusters are seemingly derived as a result of sterically reduced accessibility to glycan processing enzymes, and limited amino acid diversification around these sites supports their role protecting against the humoral immune response. Combined, our data provide a structure-based blueprint for understanding how glycans render the glycoprotein spikes of Lassa virus and other Old World arenaviruses immunologically resistant targets.
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