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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Fera D,Lee MS,Wiehe K,Meyerhoff RR,Piai A,Bonsignori M,Aussedat B,Walkowicz WE,Ton T,Zhou JO,Danishefsky S,Haynes BF,Harrison SC

doi

10.1038/s41467-018-03565-6

subject

Has Abstract

pub_date

2018-03-16 00:00:00

pages

1111

issue

1

issn

2041-1723

pii

10.1038/s41467-018-03565-6

journal_volume

9

pub_type

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