UMMS Affiliation

Program in Molecular Medicine; Department of Biochemistry and Molecular Pharmacology

Publication Date

11-7-2016

Document Type

Article

Disciplines

Biochemistry, Biophysics, and Structural Biology | Immunology and Infectious Disease | Microbiology

Abstract

The conformation of HIV-1 envelope (Env) glycoprotein trimers is key in ensuring protection against waves of neutralizing antibodies generated during infection, while maintaining sufficient exposure of the CD4 binding site (CD4bs) for viral entry. The CD4 binding loop on Env is an early contact site for CD4 while penetration of a proximal cavity by CD4 triggers Env conformational changes for entry. The role of residues in the CD4 binding loop in regulating the conformation of the trimer and trimer association domain (TAD) was investigated using a novel saturation mutagenesis approach. Single mutations identified, resulted in distinct trimer conformations affecting CD4bs exposure, the glycan shield and the TAD across diverse HIV-1 clades. Importantly, mutations that improve access to the CD4bs without exposing the immunodominant V3 loop were identified. The different trimer conformations identified will affect the specificity and breadth of nabs elicited in vivo and are important to consider in design of Env immunogens for vaccines.

Rights and Permissions

Copyright: © 2016 Duenas-Decamp et al. Citation: PLoS Pathog. 2016 Nov 7;12(11):e1005988. doi: 10.1371/journal.ppat.1005988. eCollection 2016. Link to article on publisher's site

DOI of Published Version

10.1371/journal.ppat.1005988

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

PLoS pathogens

PubMed ID

27820858

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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