HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope Journal Article

Authors: Fera, D.; Lee, M. S.; Wiehe, K.; Meyerhoff, R. R.; Piai, A.; Bonsignori, M.; Aussedat, B.; Walkowicz, W. E.; Ton, T.; Zhou, J. O.; Danishefsky, S.; Haynes, B. F.; Harrison, S. C.
Article Title: HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope
Abstract: HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide ("Man9-V3") for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutralizing antibody (bnAb) lineage ("DH270"), to visualize the epitope on Env and to study how affinity maturation of the lineage proceeded. Unlike many previous V3 mimetics, Man9-V3 encompasses two key features of the V3 region recognized by V3-glycan bnAbs-The conserved GDIR motif and the N332 glycan. In our structure of an antibody fragment of a lineage member, DH270.6, in complex with the V3 glycopeptide, the conformation of the antibody-bound glycopeptide conforms closely to that of the corresponding segment in an intact HIV-1 Env trimer. An additional structure identifies roles for two critical mutations in the development of breadth. The results suggest a strategy for use of a V3 glycopeptide as a vaccine immunogen. © 2018 The Author(s).
Keywords: unclassified drug; genetics; mutation; nonhuman; human immunodeficiency virus infection; protein conformation; protein motif; immune system; peptide; virology; immunology; chemistry; epitope mapping; epitope; crystal structure; models, molecular; human immunodeficiency virus; antibody; vaccine; glycopeptide; molecular model; hiv infections; human immunodeficiency virus 1; amino acid motifs; hiv-1; epitopes; maturation; neutralizing antibody; antibodies, neutralizing; glycan; hiv antibodies; virus envelope protein; antibody structure; humans; human; article; human immunodeficiency virus antibody; gene products, env; v 3 glycopeptide
Journal Title: Nature Communications
Volume: 9
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2018-03-16
Start Page: 1111
Language: English
DOI: 10.1038/s41467-018-03565-6
PUBMED: 29549260
PROVIDER: scopus
PMCID: PMC5856820
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
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