Journal
IMMUNOLOGICAL REVIEWS
Volume 275, Issue 1, Pages 21-32Publisher
WILEY
DOI: 10.1111/imr.12507
Keywords
cryo-electron microscopy; epitope mapping; glycan shield; HIV envelope structure; structure-based vaccine design; x-ray crystallography
Categories
Funding
- NIH [P01 AI110657, R01 AI084817]
- Collaboration for AIDS Vaccine Discovery [OPP1084519, OPP1115782]
- Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery [UM1 AI100663]
- Bill and Melinda Gates Foundation
- Skaggs Institute
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P01AI110657, R01AI084817, UM1AI100663, R56AI084817] Funding Source: NIH RePORTER
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Structure determination of the HIV-1 envelope glycoprotein (Env) presented a number of challenges, but several high-resolution structures have now become available. In 2013, cryo-EM and x-ray structures of soluble, cleaved SOSIP Env trimers from the clade A BG505 strain provided the first glimpses into the Env trimer fold as well as more the variable regions. A recent cryo-EM structure of a native full-length trimer without any stabilizing mutations had the same core structure, but revealed new insights and features. A more comprehensive and higher resolution understanding of the glycan shield has also emerged, enabling a more complete representation of the Env glycoprotein structure. Complexes of Env trimers with broadly neutralizing antibodies have surprisingly illustrated that most of the Env surface can be targeted in natural infection and that the neutralizing epitopes are almost all composed of both peptide and glycan components. These structures have also provided further evidence of the inherent plasticity of Env and how antibodies can exploit this flexibility by perturbing or even stabilizing the trimer to facilitate neutralization. These breakthroughs have stimulated further design and stabilization of Env trimers as well as other platforms to generate trimers that now span multiple subtypes. These Env trimers when used as immunogens, have led to the first vaccine-induced neutralizing antibodies for structural and functional analyses.
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